A Retrospective Analysis of the Clinicopathological Profile of Oral Squamous Cell Carcinoma in Tobacco and Non-tobacco Users: Highlighting the Significance of Chronic Mechanical Irritation.

BACKGROUND AND AIM: Oral squamous cell carcinoma (OSCC) is among the leading top three cancers in India. However, recent literature has shown an increase in the rise of oral cancer in younger individuals without any history of tobacco-related habits. Chronic mucosal irritation (CMI) has been noted to have a substantial impact on the development and etiology of OSCC. With the shift in the trend, it is imperative to observe and monitor alterations associated with its etiological factors. The study aims to evaluate the prevalence and clinical characteristics of OSCC patients and the association of these parameters in cases with and without tobacco usage. METHODOLOGY: A retrospective study spanning a period of 10 years was done on histopathologically diagnosed cases of OSCC. Various clinicopathological characteristics were collected from patient records, including demographic features, tobacco-related habits, including tobacco chewing and smoking, clinical presentation, anatomic sites, and histopathological grading based on the inclusion and exclusion criteria. The data were tabulated to Microsoft Excel (Microsoft Corporation, Redmond, WA), and descriptive statistics analysis and chi-square test of significance were applied to the data using IBM SPSS Statistics (version 29.0.2; IBM Corp., Armonk, NY). The study correlated the epidemiologic behavior of OSCC with age, gender, site, and tobacco-related habits. RESULTS: This study included a sample size of 204 (72 females & 132 males). Tobacco-related habit-associated cases were 98 (48.5%) and without tobacco habits were 61 cases (29.6%). Etiology associated with CMI emerged to be a significant tooth-related factor. Out of 72 females, 32 (44.4%) of the females were without habit. OSCC caused by trauma from CMI was analyzed in 40 cases (19.6%) and 22 (55%) were females. The majority of lesions (76 (37.4%) cases) presented on the lateral border of the tongue. Among the OSCC patients with a history of chronic mechanical irritation, 37 (48.7%) cases were observed to be specifically on the lateral border of the tongue. CONCLUSION: These 10-year data will generate awareness about the disease pattern occurring within a community and provide an overview of the prerequisite of considering CMI as an etiological factor for the development of OSCC without the association of tobacco-related habits.

MicroRNA-510-3p regulated vascular dysfunction in Preeclampsia by targeting Vascular Endothelial Growth Factor A (VEGFA) and its signaling axis.

INTRODUCTION: Preeclampsia (PE) is a pregnancy complication associated with multi-organ damage and vascular dysfunction. Meanwhile, microRNAs or miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in the PE patients' blood compared to normal. Hence, we hypothesize that miR-510-3p targets Vascular endothelial growth factor A (VEGFA) in the regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential therapeutic target for PE. METHODS: The proliferation, migration, and apoptosis of HTR8/SVNeo and BeWo cells were analyzed by manipulating the miR-510-3p and VEGFA expression. Similarly, the inhibition of miR-510-3p through anti-miR-510-3p was analyzed in PE rat models, and the biochemical, hemodynamic parameters, and histopathology were examined between the groups. Moreover, the expression of miR-510-3p and VEGFA/PI3K/AKT/eNOS/mTOR axis was analyzed using qRT-PCR and Western blot. RESULTS: Significant changes were observed in the BP, proteinuria, and other biochemical parameters between PE and control rats. Our results suggest that miR-510-3p targets VEGFA leading to vascular dysfunction in PE, while treatment with anti-miR-510-3p in the PE-induced rat model exhibits a significant change in the expression of miR-510-3p/VEGFA/PI3K/AKT/eNOS/mTOR signaling where miR-510-3p showed lesser expression and vice versa with VEGFA. The gene and protein expression analysis revealed a significant correlation between miR-510-3p and the VEGFA signaling axis in PE. DISCUSSION: Thus, our findings from in vitro and in vivo suggest miR-510-3p as a potential therapeutic target and anti-miR-510-3p as a novel therapeutic molecule for PE.

Advancements in microRNA-based electrochemical biosensors for preeclampsia detection.

Highlighting a recently proposed mechanism for early detection of preeclampsia using microRNA-based electrochemical biosensors, showcasing their transformative potential for improved prenatal care.

microRNAs and their therapeutic strategy in phase I and phase II clinical trials.

miRNAs play a crucial therapeutic role in diseases such as cancer, diabetes and viral infections, with around 1900 identified in the human genome. Some have progressed to clinical trials, and miRNA mimics and miRNA inhibitors are pivotal therapeutic molecules undergoing evaluation. The review delves into various miRNA-associated clinical trials, emphasizing their precision in targeting specific genes, modulating disease pathways and diagnostic potential. This underscores the importance of miRNA therapy, foreseeing innovations in precision medicine techniques for diverse diseases. The future envisions improved delivery systems addressing challenges like immunogenicity and digestion, while a comprehensive miRNA-based omics database could guide the development of tailored antisense miRNAs, further advancing precision medicine strategies.

Expression profiling of signal transducer and activator of transcription3 in oral squamous cell carcinoma in south Indian population.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is widely acknowledged as the most prevalent form of oral malignancy. The annual identification of approximately 540,000 new cases of OSCC highlights its significant impact. The survival rate beyond 5 years postsurgery remains low. The role of signal transducer and activator of transcription3 (STAT3), a signaling protein involved in various cellular processes, has garnered attention. Aberrant activation of STAT3 has been implicated in OSCC progression and aggressiveness. Understanding the impact of STAT3 dysregulation on OSCC outcomes could provide valuable insights for developing targeted therapies. The aim of this study was to evaluate and compare the expression levels of STAT3 in OSCC and normal tissues of the same patients. METHODS: The expression levels of STAT3 in 63 OSCC samples were detected by qRT-PCR and compared to patient-matched-non-tumor oral tissues. Data were normalized to internal controls, and fold change in STAT3 expression was calculated using the ∆∆Ct method. Correlations between expression level and clinicopathologic characteristics like staging and grading of OSCC samples were also analyzed. RESULTS: Our findings demonstrated that STAT3 expression was significantly upregulated (P<0.0001) in OSCC patients compared to normal control tissue. Furthermore, we also observed a positive correlation between elevated STAT3 expression and higher OSCC histological grades when compared to the normal tissue. Well differentiated OSCC showed a slightly lower expression compared to the other two grades. CONCLUSIONS: Our results support the involvement of STAT3 in OSCC tumorigenesis. We propose that STAT3 might be used as a potential biomarker for OSCC. Further investigations are warranted to elucidate the mechanistic basis for the observed associations and to explore STAT3's potential as a therapeutic target in OSCC.

MicroRNA-34a-3p and its target tumor necrosis factor-α in the regulation of South Indian oral squamous cell carcinoma population.

BACKGROUND: The most frequent head and neck cancer is oral squamous cell carcinoma (OSCC), the common histological cancer of the oral cavity and is one of the most prevalent forms of cancer globally. It has been known that there are several biomarkers and therapeutic targets that have been discovered for OSCC, but none of them were effective against the progression of OSCC. Interestingly, small non-coding RNAs termed microRNAs (miRNAs) regulate cellular activity by targeting numerous signaling pathways or genes that either promote or repress the progression of diseases. Surprisingly, among the differentially expressed miRNAs, miR-34a was identified to be highly sensitive and specific to OSCC and widely studied for its role in various cancers, including OSCC. METHODS: The secondary structure of miR-34a-3p was analyzed using bioinformatic analysis and its targets were screened using the TargetScan database. Specimens of 25 OSCC cancer tissues and adjacent normal tissues were collected from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals. The tissues were processed for H&E staining and gene expression analysis of miR-34a-3p and tumor necrosis factor alpha (TNF-α). RESULTS: The minimum free energy for miR-34a-3p was found to be -47.20 kCal which proved the stability of the miRNA. The histopathological examination confirmed the OSCC cases and the gene expression analysis revealed that miR-34a-3p was significantly downregulated in OSCC tissues, whereas TNF-α showed vice versa expression. CONCLUSIONS: miR-34a-3p could be postulated as a potential therapeutic target for OSCC.

Inflammation in smokers and non-smokers during implant surgery among Indians.

One of the main drawbacks faced by the dental implant surgeons is to assess the healing of the tissues and implant success for patients who are smokers. It is of interest to evaluate inflammatory biomarkers to understand the soft and hard tissue healing between smokers and non-smokers based on levels of IL-6 and STAT-3. This study included totally 20 patients (Group 1 : smokers (n=10) and Group 2: non-smokers (n=10)) undergoing stage-1 implant surgery and collected a tissue sample for the patients to assess the levels of IL-6 and STAT-3. The results indicated that there is a pronounced increase in the biomarkers in patients who are smokers in comparison to non-smokers.

Relevance of micro-RNAs and their targets as a diagnostic and prognostic marker in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) ranks sixth among all cancers in the world, affecting various sites of the oral cavity with associated several risk factors. High mortality has been associated with the presence of metastasis during the time of diagnosis and an increase in therapeutic relapses. Micro-RNAs (miRNAs) are a group of small non-coding RNAs with salient roles in the initiation and progression of cancer. The tumorigenesis of OSCC is associated with the dysregulation of several miRNAs. MicroRNAs are an area of recent interest, and numerous studies have been reported and are being undertaken to identify their role in diagnostic and prognostic value for oral cancers. Most of the miRNA processing machinery is considered to be either up-/down-regulated in OSCC, but the underlying mechanism of miRNA dysregulation and their activity as either a tumour suppressor or an oncogene in oral carcinogenesis is not yet clear. The article presents a concise review of the available current literature regarding the various miRNAs' signatures in OSCC and their role as diagnostic/prognostic biomarkers.

Expression levels of microRNA-7110 in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, and it is responsible for more than 95% of head and neck cancers. Despite advancements in research and treatment, patient's survival has not significantly increased in recent years. On the other hand, microRNAs (miRNAs) are a major class of small non-coding RNAs that regulate gene expression of the target mRNAs. Thus, understanding the mechanisms behind OSCC formation and progression may lead to the identification of potential diagnostic biomarkers and therapeutic molecules for the treatment of OSCC. The aim of the current study was to analyze expression levels of miR-7110 in OSCC tissues and adjacent normal tissues as it could provide insights into its potential role in OSCC development or progression as a valuable biomarker. METHODS: A total of 20 OSCC and adjacent normal tissues were collected from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals (Chennai, India). The tissues were processed for hematoxylin and eosin staining and expression studies. The data were shown as mean±standard deviation and P<0.05 was considered statistically significant. RESULTS: Our histopathological observations revealed an invasive malignant epithelial neoplasm with malignant epithelial cells exhibiting features of severe epithelial dysplasia invading the connective tissue stroma as islands, strands and cords with varying degrees of differentiation. Our results have also revealed that the expression levels of miR-7110 were found to be significantly higher in OSCC samples when compared to the normal tissue. CONCLUSIONS: We can preliminarily conclude that based on the increased expression of miR-7110 in OSCC tissue samples, they can be used as an early diagnostic or prognostic biomarker and/or a therapeutic target for the treatment of OSCC even though more focused research in that direction is needed.

Gene expression analysis of microRNA-1285 in the South Indian oral squamous cell carcinoma population.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common oral malignant tumor, which has poor prognosis. The traditional investigative modality is invasive biopsy which is the gold standard for diagnosis. In recent years, alternative methods like non-invasive biomarkers have been studied for their potential role in early diagnosis and prognosis. Among them, microRNAs (miRNAs or miRs) are short non-coding RNAs that regulate gene expression in various diseases, including OSCC. Several miRNAs are being researched as non-invasive biomarkers as well as novel therapeutic targets in the treatment of OSCC. MiR expression can be upregulated or downregulated in OSCC. Among the reported miRNAs, miR-1285 is an important miRNA found to be involved in OSCC. The aim of the current study was to quantify the levels of miR-1285 in OSCC samples and to validate their potential role as biomarkers for OSCC detection. METHODS: Sixteen samples of cancer tissue and normal tissue were evaluated from a total of 25 patients, in the study, conducted in the Department of Oral and Maxillofacial Surgery. The tissues were processed for H&E staining and gene expression analysis of miR-1285. The samples were collected after proper informed consent from the patients. Total RNA isolated was reverse transcribed into cDNA which was used in the gene expression analysis using qRT-PCR. RESULTS: The histopathological examination confirmed the OSCC cases and the gene expression analysis revealed that miR-1285 was significantly downregulated in OSCC tissues. Since miR-1285 showed significant difference between the OSCC and normal tissues it could be postulated as a potential biomarker and therapeutic target for OSCC. CONCLUSIONS: Further in-vitro and in-vivo studies could validate their functional role in OSCC.

Prospective study: expression levels of microRNA-7-3p and its target STAT3 in head and neck cancer.

BACKGROUND: Head and neck cancer (HNC) is the seventh most prevalent type of cancer in the globe, and it encompasses a wide range of tumors that affect the oral, facial and neck region. Despite breakthroughs in treatment strategies, patients survival has not increased substantially in the last few decades. Therefore, there is need for quick and reliable biomarkers and therapeutic targets for the treatment of HNC. Interestingly, microRNAs (miRNAs) are a small non-coding RNAs (ncRNAs) that have a role in the post-transcriptional regulation of gene expression. Thus, the aim of the study is to evaluate the role of miR-7-3p in the HNC and normal tissues. METHODS: A total of 25 HNC and normal tissues were collected from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals. Bioinformatic tool (TargetScan) was used to predict the target for miR-7-3p. The tissue samples were processed for Hematoxylin and Eosin staining and following that total RNA was extracted and analyzed for expression studies using RT-qPCR. RESULTS: The bioinformatic analysis of the current study have revealed that STAT3 is a direct target for miR-7-3p. The histopathological examination showed damaged epithelial cells and keratin pool formation was observed in HNC tissue. Our results have also revealed that the miR-7-3p levels were significantly reduced and STAT3 levels were significantly higher in the HNC tissues when compared to the normal tissues. CONCLUSIONS: MiR-7-3p can be used as a prognostic, diagnostic biomarker and therapeutic target for the treatment of HNC.

MicroRNAs as important players in regulating cancer through PTEN/PI3K/AKT signalling pathways.

Cancer being the leading cause of mortality has become a great threat worldwide. Current cancer therapeutics lack specificity and have side effects due to a lack of understanding of the molecular mechanisms and signalling pathways involved in carcinogenesis. In recent years, researchers have been focusing on several signalling pathways to pave the way for novel therapeutics. The PTEN/PI3K/AKT pathway is one of the important pathways involved in cell proliferation and apoptosis, leading to tumour growth. In addition, the PTEN/PI3K/AKT axis has several downstream pathways that could lead to tumour malignancy, metastasis and chemoresistance. On the other hand, microRNAs (miRNAs) are important regulators of various genes leading to disease pathogenesis. Hence studies of the role of miRNAs in regulating the PTEN/PI3K/AKT axis could lead to the development of novel therapeutics for cancer. Thus, in this review, we have focused on various miRNAs involved in the carcinogenesis of various cancer via the PTEN/PI3K/AKT axis.

Diagnostic and Therapeutic Application of Exosomal microRNAs Inducing Inflammation in Type 2 Diabetes Mellitus.

Diabetes mellitus is a class of noncommunicable chronic metabolic disorders marked by hyperglycemia due to insulin production, insulin action or both and has reached epidemic levels around the world. The two most frequent types of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Despite substantial improvements in the knowledge and treatment of DM, the associated incidence and mortality rates remain steadily increased. Reliable markers for the early detection, monitoring and focused treatment of DM are desperately required. Conversely, microRNAs (miRNAs) have received much significance due to their regulatory involvement in gene expression. Fascinatingly, exosomes can be enclosed into miRNAs to transport or distribute them into the target cells or tissues in which they have a physiological regulatory action. Thus, exosomal miRNAs are proving to be important regulators in the establishment and maintenance of DM, however, further mode of action will be needed to investigate in order to fully comprehend the pathophysiological process. Hereby, this review outlines the recent findings on the role of exosomal miRNAs intending to understand the precise function in diagnostic and therapeutic aspects in T2DM disease.