Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 5.318
Filter
2.
Head Face Med ; 20(1): 37, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890650

ABSTRACT

BACKGROUND: The treatment of oral squamous cell carcinoma (OSCC) remains challenging and survival rates have not been improved significantly over the past decades. Integrins have been recognized driving the cancer progression and high expression levels cause poor outcomes in patients afflicted with OSCC. Integrin αvß6 and its subunit integrin beta 6 (ITGB6) were discovered to enhance the invasiveness by providing beneficial effects on downstream pathways promoting the cancer progression. The objective of this study was to establish a CRISPR/Cas9-mediated knock out of ITGB6 in the human OSCC cell line HN and investigate the effects on the migration and proliferation ability. METHODS: ITGB6 knock out was performed using the CRISPR/Cas9-system, RNPs, and lipofection. Monoclonal cell clones were achieved by limiting dilution and knock out verification was carried out by sanger sequencing and FACS on protein level. The effects of the knock out on the proliferation and migration ability were evaluated by using MTT and scratch assays. In addition, in silico TCGA analysis was utilized regarding the effects of ITGB6 on overall survival and perineural invasion. RESULTS: In silico analysis revealed a significant impact of ITGB6 mRNA expression levels on the overall survival of patients afflicted with OSCC. Additionally, a significantly higher rate of perineural invasion was discovered. CRISPR/Cas9-mediated knock out of ITGB6 was performed in the OSCC cell line HN, resulting in the generation of a monoclonal knock out clone. The knock out clone exhibited a significantly reduced migration and proliferation ability when compared to the wildtype. CONCLUSIONS: ITGB6 is a relevant factor in the progression of OSCC and can be used for the development of novel treatment strategies. The present study is the first to establish a monoclonal CRISPR/Cas9-mediated ITGB6 knockout cell clone derived from an OSCC cell line. It suggests that ITGB6 has a significant impact on the proliferative and migratory capacity in vitro.


Subject(s)
CRISPR-Cas Systems , Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Integrin beta Chains , Mouth Neoplasms , Humans , Cell Movement/genetics , Cell Proliferation/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Cell Line, Tumor , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Integrin beta Chains/genetics , Gene Knockout Techniques , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Neoplasm Invasiveness/genetics , Gene Expression Regulation, Neoplastic
3.
Cells ; 13(11)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38891124

ABSTRACT

Canine oral melanoma is the most prevalent malignant tumor in dogs and has a poor prognosis due to its high aggressiveness and high metastasis and recurrence rates. More research is needed into its treatment and to understand its pathogenic factors. In this study, we isolated a canine oral mucosal melanoma (COMM) cell line designated as COMM6605, which has now been stably passaged for more than 100 generations, with a successful monoclonal assay and a cell multiplication time of 22.2 h. G-banded karyotype analysis of the COMM6605 cell line revealed an abnormal chromosome count ranging from 45 to 74, with the identification of a double-armed chromosome as the characteristic marker chromosome of this cell line. The oral intralingual and dorsal subcutaneous implantation models of BALB/c-nu mice were successfully established; Melan-A (MLANA), S100 beta protein (S100ß), PNL2, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) were stably expressed positively in the canine oral tumor sections, tumor cell lines, and tumor sections of tumor-bearing mice. Sublines COMM6605-Luc-EGFP and COMM6605-Cherry were established through lentiviral transfection, with COMM6605-Luc-EGFP co-expressing firefly luciferase (Luc) and enhanced green fluorescent protein (EGFP) and COMM6605-Cherry expressing the Cherry fluorescent protein gene. The COMM6605-Luc-EGFP fluorescent cell subline was injected via the tail vein and caused lung and lymph node metastasis, as detected by mouse live imaging, which can be used as an animal model to simulate the latter steps of hematogenous spread during tumor metastasis. The canine oral melanoma cell line COMM6605 and two sublines isolated and characterized in this study can offer a valuable model for studying mucosal melanoma.


Subject(s)
Melanoma , Mouth Mucosa , Mouth Neoplasms , Animals , Dogs , Melanoma/pathology , Melanoma/genetics , Melanoma/veterinary , Mouth Neoplasms/pathology , Mouth Neoplasms/genetics , Mouth Neoplasms/veterinary , Cell Line, Tumor , Mouth Mucosa/pathology , Mouth Mucosa/metabolism , Mice , Mice, Inbred BALB C , Disease Models, Animal , Mice, Nude
4.
BMC Cancer ; 24(1): 731, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877482

ABSTRACT

BACKGROUND: This study sought to investigate the prognostic value of basement membrane (BM)-associated gene expressions in oral cancer. METHODS: We harvested and integrated data on BM-associated genes (BMGs), the oral cancer transcriptome, and clinical information from public repositories. After identifying differentially expressed BMGs, we used Cox and Lasso regression analyses to create a BMG-based risk score for overall survival at various intervals. We then validated this score using the GSE42743 cohort as a validation set. The prognostic potential of the risk scores and their relations to clinical features were assessed. Further, we conducted functional pathway enrichment, immune cell infiltration, and immune checkpoint analyses to elucidate the immunological implications and therapeutic potential of the BMG-based risk score and constituent genes. To confirm the expression levels of the BMG LAMA3 in clinical samples of oral cancer tissue, we performed quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. RESULTS: The BMGs LAMA3, MMP14, and GPC2 demonstrated notable prognostic significance, facilitating the construction of a BMG-based risk score. A higher risk score derived from BMGs correlated with a poorer survival prognosis for oral cancer patients. Moreover, the risk-associated BMGs exhibited a significant relationship with immune function variability (P < 0.05), discrepancies in infiltrating immune cell fractions, and immune checkpoint expressions (P < 0.05). The upregulated expression levels of LAMA3 in oral cancer tissues were substantiated through qRT-PCR and immunohistochemical staining. CONCLUSION: The BMG-based risk score emerged as a reliable prognostic tool for oral cancer, meriting further research for validation and potential clinical application.


Subject(s)
Basement Membrane , Biomarkers, Tumor , Mouth Neoplasms , Humans , Mouth Neoplasms/genetics , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Prognosis , Basement Membrane/metabolism , Basement Membrane/pathology , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Transcriptome , Female , Gene Expression Profiling , Male , Laminin/genetics
5.
BMC Cancer ; 24(1): 738, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879503

ABSTRACT

OBJECTIVE: Single nucleotide polymorphisms (SNPs) are common in genes and can lead to dysregulation of gene expression in tissues, which can affect carcinogenesis. Many studies reporting the association between xeroderma pigmentosum group D (XPD) polymorphisms of rs13181 and rs1799793 with oral cancer risk, but with conflicting and inconclusive results. METHODS: We performed a comprehensive and systematic search through the PubMed, Elsevier, Web of science, and Embase databases, twelve studies were included in the meta-analysis to determine whether XPD rs13181 and rs1799793 polymorphism contributed to the risk of oral cancer. RESULTS: The pooled date indicated a significant association between the rs13181 polymorphism and oral cancer risk for the allele comparison model (odds ratio, OR = 1.60, 95% confidence intervals, CI = 1.09-2.35, P = 0.02), the dominant model (OR = 1.74, 95% CI = 1.08-2.82, P = 0.02), and the heterozygote model (OR = 1.59, 95% CI = 1.02-2.49, P = 0.04). For the XPD rs1799793 polymorphism, it is not associated with the incidence of oral cancer under any model. Subgroup analyses based on ethnicity indicated that the rs13181 polymorphism increased the risk of oral cancer among Asians according to the allele comparison model (OR = 1.97, 95% CI = 1.10-3.51, P = 0.02), the dominant model (OR = 2.35, 95% CI = 1.25-4.44, P = 0.008), the heterozygote model (OR = 2.05, 95% CI = 1.15-3.66, P = 0.01), and the homozygous model (OR = 2.47, 95% CI = 1.06-5.76, P = 0.04). CONCLUSION: Our meta-analysis suggests a positive correlation between XPD rs13181polymorphism and the development of oral cancer among Asians, but a negative correlation among Caucasians populations.


Subject(s)
Genetic Predisposition to Disease , Mouth Neoplasms , Polymorphism, Single Nucleotide , Xeroderma Pigmentosum Group D Protein , Humans , Mouth Neoplasms/genetics , Xeroderma Pigmentosum Group D Protein/genetics , Odds Ratio , Alleles , Asian People/genetics , Risk Factors
6.
Cell Death Dis ; 15(5): 376, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811531

ABSTRACT

The tumor margin as the invasive front has been proven to be closely related to the progression and metastasis of oral squamous cell carcinoma (OSCC). However, how tumor cells in the marginal region obtain the extra energy needed for tumor progression is still unknown. Here, we used spatial metabolomics and the spatial transcriptome to identify enhanced energy metabolism in the tumor margin of OSCC and identified that the downregulation of Ras-related glycolysis inhibitor and calcium channel regulator (RRAD) in tumor cells mediated this process. The absence of RRAD enhanced the ingestion of glucose and malignant behaviors of tumor cells both in vivo and in vitro. Mechanically, the downregulation of RRAD promoted the internal flow of Ca2+ and elevated its concentration in the nucleus, which resulted in the activation of the CAMKIV-CREB1 axis to induce the transcription of the glucose transporter GLUT3. GLUT inhibitor-1, as an inhibitor of GLUT3, could suppress this vigorous energy metabolism and malignant behaviors caused by the downregulation of RRAD. Taken together, our study revealed that enhanced energy metabolism in the tumor margin mediated by RRAD promotes the progression of OSCC and proved that GLUT3 is a potential target for future treatment of OSCC.


Subject(s)
Carcinoma, Squamous Cell , Disease Progression , Energy Metabolism , Mouth Neoplasms , Humans , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Animals , Cell Line, Tumor , Mice , Mice, Nude , Gene Expression Regulation, Neoplastic , Glucose Transporter Type 3/metabolism , Glucose Transporter Type 3/genetics , Mice, Inbred BALB C , Glucose/metabolism , Calcium/metabolism , Glycolysis
7.
Anticancer Res ; 44(6): 2517-2531, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821588

ABSTRACT

BACKGROUND/AIM: Despite advances in oral squamous cell carcinoma (OSCC) diagnosis and treatment, the five-year survival rate remains low, underscoring the need for improved biomarkers and therapeutic strategies. This study investigated the role of let-7d-5p microRNA (miRNA) and its target gene OLR1 in OSCC, focusing on their implications in tumor progression, metastasis and potential as therapeutic targets. MATERIALS AND METHODS: Employing next-generation sequencing and bioinformatic tools, we profiled differentially expressed miRNAs in metastatic OSCC cell lines, identifying let-7d-5p as a key down-regulated miRNA and OLR1 as a novel target of let-7d-5p. We validated this interaction using luciferase reporter assays and studied the biological effects of modulating let-7d-5p and OLR1 expression on OSCC cell proliferation, migration, invasion, and stemness. Additionally, we analyzed clinical data to establish the relevance of OLR1 expression in OSCC prognosis. RESULTS: Our findings revealed let-7d-5p as a potent suppressor of OSCC metastasis, primarily by targeting and down-regulating OLR1. OLR1-silencing reduced OSCC cell invasiveness, migration, and stemness, indicating its prominent role in tumor progression. Mechanistically, let-7d-5p modulates a signaling cascade involving FAK, SRC, PAXILLIN, and p53, influencing cellular apoptosis and chemoresistance. Clinically, elevated OLR1 expression significantly correlates with advanced OSCC stages and poorer survival rates, highlighting its potential as a prognostic marker and therapeutic target. CONCLUSION: Our study uncovers the significance of the let-7d-5p-OLR1 axis in OSCC pathogenesis, offering novel insights for future therapeutic interventions.


Subject(s)
Carcinoma, Squamous Cell , Cell Proliferation , Disease Progression , Focal Adhesion Kinase 1 , Gene Expression Regulation, Neoplastic , MicroRNAs , Mouth Neoplasms , Signal Transduction , Tumor Suppressor Protein p53 , Humans , Mouth Neoplasms/pathology , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Prognosis , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , Signal Transduction/genetics , Cell Line, Tumor , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Proliferation/genetics , Cell Movement/genetics
8.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 145-149, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38814222

ABSTRACT

The purpose of this study was to investigate the expression of CD109 and its clinicopathological significance in oral squamous cell carcinoma. Data from TIMER2.0 and UALCAN were analyzed to assess CD109 mRNA levels in OSCC. The immunohistochemical method was used to investigate the expressions of CD109 in 20 normal oral mucosa and 75 OSCC and analyzed the relationship between the expression of CD109 and the clinical variables. The mRNA levels of CD109 in OSCC tissues were significantly higher than in adjacent normal tissues (p<0.05). Immunohistochemical analysis revealed that CD109 protein expression was increased in OSCC tissues compared to normal tissues, and this difference was statistically significant (P<0.05). The positive rate of CD109 expression was 94% (16/117) in the group with lymph node metastasis, while it was 55% (32/58) in the group without metastasis (P<0.05). Similarly, the positive rate of CD109 expression was 91% (22/23) in the low differentiation group and 59% (26/52) in the high differentiation group (P<0.05). CD109 expression is markedly higher in OSCC, contributes to the pathological grading of OSCC and predicts lymph node metastasis.


Subject(s)
Antigens, CD , Carcinoma, Squamous Cell , GPI-Linked Proteins , Lymphatic Metastasis , Mouth Neoplasms , Neoplasm Proteins , Humans , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Female , Male , Antigens, CD/metabolism , Antigens, CD/genetics , Middle Aged , GPI-Linked Proteins/metabolism , GPI-Linked Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/biosynthesis , Immunohistochemistry , Gene Expression Regulation, Neoplastic , Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Adult , Mouth Mucosa/metabolism , Mouth Mucosa/pathology , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Clinical Relevance
9.
Cancer Genet ; 284-285: 48-57, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729078

ABSTRACT

Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185-5 p and that miR-185-5 p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185-5 p/PLOD1/Akt/mTOR pathway activity.


Subject(s)
Cell Movement , Cell Proliferation , MicroRNAs , Mouth Neoplasms , Neoplasm Invasiveness , Proto-Oncogene Proteins c-akt , RNA, Long Noncoding , TOR Serine-Threonine Kinases , Humans , MicroRNAs/genetics , RNA, Long Noncoding/genetics , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Cell Movement/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Cell Proliferation/genetics , Mice , Animals , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism , Cell Line, Tumor , Signal Transduction/genetics , Gene Expression Regulation, Neoplastic , Female , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Male , Prognosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Mice, Nude
10.
Anticancer Res ; 44(6): 2369-2376, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821622

ABSTRACT

BACKGROUND/AIM: This study aimed at the analogous detection of PIK3CA mutations, common in oral squamous cell carcinoma (OSCC), in matched tumor and saliva samples. PATIENTS AND METHODS: Tissue and saliva samples were obtained from 29 patients diagnosed with primary OSCC. Saliva samples were obtained preoperatively; tissue specimens were acquired during tumor resection. Tumor DNA was extracted from both tissue and saliva samples. All samples were controlled for DNA quantity and quality and genetic matching of sample pairs was confirmed using the iPlex Pro Exome QC Panel. Variant detection was performed using the MassARRAY® System, a mass-spectrometry based detection system. Mutational analysis in tissue tumor DNA was made using the multiplexed ClearSEEK™ PIK3CA v1.0 Panel covering 20 hotspot mutations in PIK3CA. In saliva samples, variants were analyzed using both the ClearSEEK™ and the UltraSEEK® Lung v1.1 Panel, with a higher limit of detection but covering less PIK3CA variants. RESULTS: Overall, a PIK3CA variant was found in seven of the 29 tumor tissue samples (24%) by ClearSEEK™; UltraSEEK® additionally confirmed the variant in four of these seven positive samples. Of the three variants not detected by UltraSEEK®, two were not included in the panel and one was included but not detected. Of the seven variants found in tissue, five could also be detected in the matching saliva samples (71%), either by utilizing ClearSEEK™ or UltraSEEK® Conclusion: The detection of PIK3CA hotspot mutations in OSCC and their simultaneous occurrence in saliva underline the potential benefit of liquid biopsies for non-invasive cancer detection and follow-up care of OSCC patients.


Subject(s)
Biomarkers, Tumor , Carcinoma, Squamous Cell , Class I Phosphatidylinositol 3-Kinases , Mouth Neoplasms , Mutation , Saliva , Humans , Class I Phosphatidylinositol 3-Kinases/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/diagnosis , Biomarkers, Tumor/genetics , Female , Male , Middle Aged , Aged , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/diagnosis , DNA Mutational Analysis/methods , Aged, 80 and over , Adult
11.
BMC Oral Health ; 24(1): 625, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807101

ABSTRACT

BACKGROUND: Oral squamous cell cancer (OSCC) is a prevalent malignancy in oral cavity, accounting for nearly 90% of oral malignancies. It ranks sixth among the most common types of cancer worldwide and is responsible for approximately 145,000 deaths each year. It is widely accepted that noncoding RNAs participate cancer development in competitive regulatory interaction, knowing as competing endogenous RNA (ceRNA) network, whereby long non-coding RNA (lncRNA) function as decoys of microRNAs to regulate gene expression. LncRNA FOXD2-AS1 was reported to exert an oncogenic role in OSCC. Nevertheless, the ceRNA network mediated by FOXD2-AS1 was not investigated yet. This study aimed to explore the effect of FOXD2-AS1 on OSCC cell process and the underlying ceRNA mechanism. METHODS: FOXD2-AS1 expression in OSCC cells were determined via reverse transcription and quantitative polymerase chain reaction. Short hairpin RNA targeting FOXD2-AS1 was transfected into OSCC cells to silence FOXD2-AS1 expression. Then, loss-of-function experiments (n = 3 each assay) were performed to measure cell proliferation, apoptosis, migration, and invasion using colony formation, TdT-mediated dUTP Nick-End Labeling, wound healing and Transwell assays, respectively. RNA binding relation was verified by RNA immunoprecipitation and luciferase reporter assays. Rescue experiments were designed to validate whether FOXD2-AS1 affects cell behavior via the gene cellular retinoic acid binding protein 2 (CRABP2). Statistics were processed by GraphPad Prism 6.0 Software and SPSS software. RESULTS: FOXD2-AS1 was significantly upregulated in Cal27 and SCC9 cells (6.8 and 6.4 folds). In response to FOXD2-AS1 knockout, OSCC cell proliferation, migration and invasion were suppressed (approximately 50% decrease) while OSCC cell apoptosis was enhanced (more than two-fold increase). FOXD2-AS1 interacted with miR-378 g to alter CRABP2 expression. CRABP2 upregulation partly rescued (*p < 0.05, **p < 0.01, ***p < 0.001) the inhibitory impact of FOXD2-AS1 depletion on malignant characteristics of OSCC cells. CONCLUSION: FOXD2-AS1 enhances OSCC malignant cell behaviors by interacting with miR-378 g to regulate CRABP2 expression.


Subject(s)
Apoptosis , Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , MicroRNAs , Mouth Neoplasms , RNA, Long Noncoding , Humans , MicroRNAs/metabolism , MicroRNAs/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Cell Proliferation/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation, Neoplastic
12.
BMC Oral Health ; 24(1): 622, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807156

ABSTRACT

BACKGROUND: C-X-C motif chemokine ligand (CXCL8), also known as interleukin-8, is a prototypical CXC family chemokine bearing a glutamic acid-leucine-arginine (ELR) motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases. METHODS: Accordingly, the PubMed, Wanfang, Scopus and Web of Science databases were searched for articles published until July 20, 2023 using the keywords 'IL-8' or 'interleukin-8' or 'CXCL8', 'polymorphism' and 'cancer' or 'tumor'. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to examine the association. The CXCL8 +781 polymorphism genotypes were assessed with a TaqMan assay. RESULTS: About 29 related publications was conducted in an effort to better understand the association between these polymorphisms and disease risk. The CXCL8 -353A/T polymorphism was associated with an increased overall cancer risk [A vs. T, odds ratio (OR) = 1.255, 95% confidence interval (CI) (1.079-1.459), Pheterogeneity = 0.449, P = 0.003]. The CXCL8 +781 T/C allele was similarly associated with a higher risk of cancer among Caucasians [TT vs. TC + CC, OR = 1.320, 95%CI (1.046-1.666), Pheterogeneity = 0.375, P = 0.019]. Furthermore, oral cancer patients carrying the CXCL8 +781 TT + TC genotypes exhibited pronounced increases in serum levels of CXCL8 as compared to the CC genotype (P < 0.01), and also shown similar trend as compared to genotype-matched normal controls (P < 0.01). Finally, several limitations, such as the potential for publication bias or heterogeneity among the included studies should be paid attention. CONCLUSION: Current study suggested that the CXCL8 -353 and +781 polymorphisms may be associated with a greater risk of cancer, which might impact cancer prevention, diagnosis, or treatment through the different expression of CXCL8. At the same time, the +781 polymorphism may further offer value as a biomarker that can aid in the early identification and prognostic evaluation of oral cancer.


Subject(s)
Genetic Predisposition to Disease , Interleukin-8 , Mouth Neoplasms , Humans , Interleukin-8/genetics , Mouth Neoplasms/genetics , Case-Control Studies , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Risk Factors
13.
Molecules ; 29(10)2024 May 20.
Article in English | MEDLINE | ID: mdl-38792263

ABSTRACT

Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs' potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.


Subject(s)
Gene Expression Regulation, Neoplastic , Mouth Neoplasms , RNA, Untranslated , Humans , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/therapy , RNA, Untranslated/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis
14.
Cancer Med ; 13(11): e7309, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38819439

ABSTRACT

INTRODUCTION: Identification of molecular biomarkers in the saliva and serum of oral cavity cancer patients represents a first step in the development of essential and efficient clinical tools for early detection and post-treatment monitoring. We hypothesized that molecular analyses of paired saliva and serum samples from an individual would likely yield better results than analyses of either serum or saliva alone. MATERIALS AND METHODS: We performed whole-transcriptome and small non-coding RNA sequencing analyses on 32 samples of saliva and serum collected from the same patients with oral squamous cell carcinoma (OSCC) and healthy controls (HC). RESULTS: We identified 12 novel saliva and serum miRNAs and a panel of unique miRNA and mRNA signatures, significantly differentially expressed in OSCC patients relative to HC (log2 fold change: 2.6-26.8; DE: 0.02-0.000001). We utilized a combined panel of the 10 top-deregulated miRNAs and mRNAs and evaluated their putative diagnostic potential (>87% sensitivity; 100% specificity), recommending seven of them for further validation. We also identified unique saliva and serum miRNAs associated with OSCC and smoking history (OSCC smokers vs. never-smokers or HC: log2 fold change: 22-23; DE: 0.00003-0.000000001). Functional and pathway analyses indicated interactions between the discovered OSCC-related non-invasive miRNAs and mRNAs and their targets, through PI3K/AKT/mTOR signaling. CONCLUSION: Our data support our hypothesis that using paired saliva and serum from the same individuals and deep sequencing analyses can provide unique combined mRNA and miRNA signatures associated with canonical pathways that may have a diagnostic advantage relative to saliva or serum alone and may be useful for clinical testing. We believe this data will contribute to effective preventive care by post-treatment monitoring of patients, as well as suggesting potential targets for therapeutic approaches.


Subject(s)
Biomarkers, Tumor , MicroRNAs , Mouth Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Saliva , Signal Transduction , TOR Serine-Threonine Kinases , Humans , Mouth Neoplasms/genetics , Mouth Neoplasms/blood , Mouth Neoplasms/metabolism , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Female , Male , Biomarkers, Tumor/genetics , Saliva/metabolism , Saliva/chemistry , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Middle Aged , MicroRNAs/genetics , MicroRNAs/blood , Transcriptome , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Aged , RNA, Small Untranslated/genetics , RNA, Small Untranslated/blood , Adult , Case-Control Studies , Sequence Analysis, RNA , RNA, Messenger/genetics , RNA, Messenger/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/metabolism
15.
BMC Oral Health ; 24(1): 588, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773401

ABSTRACT

BACKGROUND: White Sponge Nevus (WSN) is traditionally considered a benign genetic disorder affecting the oral mucosa, primarily caused by pathogenic mutations in keratin 4 (KRT4) or keratin 13 (KRT13). Despite its benign nature, recent evidence has begun to question the malignant potential of WSN. CASE PRESENTATION: We report a case involving a 70-year-old man who presented with a white lesion on the right floor of his mouth. Initial diagnostic evaluations confirmed the lesion as WSN. Over a one-year follow-up, the lesion underwent malignant transformation, evolving into local epithelial moderate-to-severe dysplasia. Exome sequencing identified a novel insertion mutation in exon 1 of the KRT4 gene, resulting in a deletion-insertion amino acid mutation involving glycine. Single-cell RNA sequencing further revealed altered epithelial proliferation and differentiation dynamics within the lesion. CONCLUSIONS: This case not only expands the known genetic spectrum of KRT4 mutations associated with WSN but also provides preliminary evidence suggesting the malignant potential of WSN. The novel pathogenic mutation in KRT4 is postulated to alter epithelial proliferation and differentiation, thereby raising concerns about the malignant transformation of WSN. Further studies are warranted to confirm these findings.


Subject(s)
Cell Transformation, Neoplastic , Keratin-4 , Leukokeratosis, Hereditary Mucosal , Humans , Male , Aged , Keratin-4/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Leukokeratosis, Hereditary Mucosal/genetics , Leukokeratosis, Hereditary Mucosal/pathology , Mutation , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Mouth Mucosa/pathology
16.
PLoS One ; 19(5): e0296565, 2024.
Article in English | MEDLINE | ID: mdl-38781195

ABSTRACT

Epigenetic silencing through methylation is one of the major mechanisms for downregulation of tumor suppressor miRNAs in various malignancies. The aim of this study was to identify novel tumor suppressor miRNAs which are silenced by DNA hypermethylation and investigate the role of at least one of these in oral squamous cell carcinoma (OSCC) pathogenesis. We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. At 5-day post-treatment, total RNA was isolated from the 5-Azacytidine and vehicle control-treated cells. The expression of 2,459 mature miRNAs was analysed between 5-Azacytidine and control-treated OSCC cells by the microRNA microarray analysis. Of the 50 miRNAs which were found to be upregulated following 5-Azacytidine treatment, we decided to work with miR-6741-3p in details for further analysis, as it showed a mean fold expression of >4.0. The results of qRT-PCR, Western blotting, and dual-luciferase reporter assay indicated that miR-6741-3p directly targets the oncogene SRSF3 at the translational level only. The tumor-suppressive role of miR-6741-3p was established by various in vitro assays and in vivo study in NU/J athymic nude mice. Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulating SRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies.


Subject(s)
Carcinoma, Squamous Cell , Gene Expression Regulation, Neoplastic , MicroRNAs , Mouth Neoplasms , Serine-Arginine Splicing Factors , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Animals , Cell Line, Tumor , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Mice , Gene Expression Regulation, Neoplastic/drug effects , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolism , DNA Methylation , Introns/genetics , Mice, Nude , Azacitidine/pharmacology , Oncogenes/genetics
17.
J Transl Med ; 22(1): 477, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38764038

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a malignant tumor with a poor prognosis. Traditional treatments have limited effectiveness. Regulation of the immune response represents a promising new approach for OSCC treatment. B cells are among the most abundant immune cells in OSCC. However, the role of B cells in OSCC treatment has not been fully elucidated. METHODS: Single-cell RNA sequencing analysis of 13 tissues and 8 adjacent normal tissues from OSCC patients was performed to explore differences in B-cell gene expression between OSCC tissues and normal tissues. We further investigated the relationship between differentially expressed genes and the immune response to OSCC. We utilized tissue microarray data for 146 OSCC clinical samples and RNA sequencing data of 359 OSCC samples from The Cancer Genome Atlas (TCGA) to investigate the role of T-cell leukemia 1 A (TCL1A) in OSCC prognosis. Multiplex immunohistochemistry (mIHC) was employed to investigate the spatial distribution of TCL1A in OSCC tissues. We then investigated the effect of TCL1A on B-cell proliferation and trogocytosis. Finally, lentiviral transduction was performed to induce TCL1A overexpression in B lymphoblastoid cell lines (BLCLs) to verify the function of TCL1A. RESULTS: Our findings revealed that TCL1A was predominantly expressed in B cells and was associated with a better prognosis in OSCC patients. Additionally, we found that TCL1A-expressing B cells are located at the periphery of lymphatic follicles and are associated with tertiary lymphoid structures (TLS) formation in OSCC. Mechanistically, upregulation of TCL1A promoted the trogocytosis of B cells on dendritic cells by mediating the upregulation of CR2, thereby improving antigen-presenting ability. Moreover, the upregulation of TCL1A expression promoted the proliferation of B cells. CONCLUSION: This study revealed the role of B-cell TCL1A expression in TLS formation and its effect on OSCC prognosis. These findings highlight TCL1A as a novel target for OSCC immunotherapy.


Subject(s)
B-Lymphocytes , Carcinoma, Squamous Cell , Gene Expression Regulation, Neoplastic , Mouth Neoplasms , Proto-Oncogene Proteins , Tertiary Lymphoid Structures , Humans , Prognosis , Mouth Neoplasms/pathology , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Mouth Neoplasms/immunology , Tertiary Lymphoid Structures/pathology , Tertiary Lymphoid Structures/immunology , Tertiary Lymphoid Structures/metabolism , B-Lymphocytes/metabolism , B-Lymphocytes/immunology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/metabolism , Female , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Male , Middle Aged , Cell Line, Tumor , Cell Proliferation
18.
JCI Insight ; 9(10)2024 May 22.
Article in English | MEDLINE | ID: mdl-38775151

ABSTRACT

Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro-tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph-circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.


Subject(s)
Carcinoma, Squamous Cell , Chemokine CX3CL1 , Lymphangiogenesis , Lymphatic Metastasis , Mouth Neoplasms , Chemokine CX3CL1/metabolism , Chemokine CX3CL1/genetics , Animals , Mouth Neoplasms/pathology , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Mice , Lymphangiogenesis/genetics , Humans , Cell Line, Tumor , Lymphatic Metastasis/pathology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Female , Tumor Microenvironment/immunology , Male
19.
Cell Cycle ; 23(5): 588-601, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38743408

ABSTRACT

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with a poor prognosis, yet the underlying mechanism needs further exploration. Non-SMC condensin I complex subunit D2 (NCAPD2) is a widely expressed protein in OSCC, but its role in tumor development is unclear. This study aimed to explore NCAPD2 expression and its biological function in OSCC. NCAPD2 expression in OSCC cell lines and tissue specimens was analyzed using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Cancer cell growth was evaluated using cell proliferation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, and colony formation assays. Cell migration was evaluated using wound healing and Transwell assays. Apoptosis was detected using flow cytometry. The influence of NCAPD2 on tumor growth in vivo was evaluated in a mouse xenograft model. NCAPD2 expression was significantly higher in OSCC than that in normal oral tissue. In vitro, the knockdown of NCAPD2 inhibited OSCC cell proliferation and promoted apoptosis. NCAPD2 depletion also significantly inhibited the migration of OSCC cells. Moreover, NCAPD2 overexpression induced inverse effects on OSCC cell phenotypes. In vivo, we demonstrated that downregulating NCAPD2 could inhibit the tumorigenicity of OSCC cells. Mechanically, OSCC regulation by NCAPD2 involved the Wnt/ß-catenin signaling pathway. These results suggest NCAPD2 as a novel oncogene with an important role in OSCC development and a candidate therapeutic target for OSCC.


Subject(s)
Apoptosis , Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Mouth Neoplasms , Wnt Signaling Pathway , Humans , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/genetics , Animals , Wnt Signaling Pathway/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cell Movement/genetics , Apoptosis/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/genetics , Mice , Mice, Nude , Disease Progression , Female , Male , Gene Expression Regulation, Neoplastic , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Mice, Inbred BALB C , beta Catenin/metabolism
20.
J Pak Med Assoc ; 74(4): 762-768, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38751274

ABSTRACT

Cancer of the oral cavity has numerous types and, among all, oral squamous cell carcinoma represents >90% of all cancers of the oral area. Oral squamous cell carcinoma arises from the squamous lining of the oral cavity. Across the globe, most commonly it develops in the regions of tongue followed by floor of the mouth, and lower lip. Neurogenic locus notch homolog protein 1 gene has its association with oral squamous cell carcinoma and is known to be associated with both oncogenic and tumour suppressor roles. The current narrative review comprised literature published from 2013 to 2023. It was searched on Google Scholar, PubMed and Google databases. Globally, neurogenic locus notch homolog protein 1 mutations are associated with the development of oral squamous cell carcinoma. Most of the mutations are linked to ligand bind epidermal growth factor-like repeat region of extracellular domain of neurogenic locus notch homolog protein 1. Once activated, the pathway is involved in tumour progression and metastasis. The Asians compared to Caucasians are more affected by neurogenic locus notch homolog protein 1 mutations.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Mutation , Receptor, Notch1 , Humans , Carcinoma, Squamous Cell/genetics , Mouth Neoplasms/genetics , Receptor, Notch1/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...