Gene alterations in the nuclear transport receptor superfamily: A study of head and neck cancer.

In cancer cells, the nuclear transport system is often disrupted, leading to abnormal localization of nuclear proteins and altered gene expression. This disruption can arise from various mechanisms such as mutations in genes that regulate nuclear transport, altered expression of transport proteins, and changes in nuclear envelope structure. Oncogenic protein build-up in the nucleus due to the disturbance in nuclear transport can also boost tumor growth and cell proliferation. In this study, we performed bioinformatic analyses of 23 key nuclear transport receptors using genomic and transcriptomic data from pancancer and head and neck squamous cell carcinoma (HNSCC) datasets from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia and found that the total alteration frequency of 23 nuclear transport receptors in 2691 samples of the PCAWG Consortium was 42.1% and a high levels of genetic alterations was significantly associated with poor overall survival. Amplification was the most common type of genetic alterations, and results in the overexpression of nuclear transport receptors in HNSCC compared to normal tissues. Furthermore, our study revealed that seven out of eight cell cycle genes (CDK1, CDK2, CDK4, CDK6, CCNA1, CCNB1, and CCNE2) were significantly and positively correlated with nuclear transport receptor genes in TCGA pancancer and CCLE datasets. Additionally, functional enrichment analysis showed that nuclear transport receptor genes were mainly enriched in the adhesion junction, cell cycle, ERBB, MAPK, MTOR and WNT signaling pathways.

Reliability of online dental final exams in the pre and post COVID-19 era: A comparative study.

Amidst the fourth COVID-19 wave in Viet Nam, national lockdowns necessitated the closure of numerous dental schools. To assess DDS (Doctor of Dental Surgery) graduation exams, this study analyzed their 2021 implementation in comparison to onsite exams conducted in 2020 and 2022 at the Faculty of Odonto-Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam (FOS-UMPH). The final online examination comprises two main sessions: a synchronous online examination using FOS-UMPH e-Learning for theories (consisting of 200 MCQs and 3 written tests with 3 clinical situations needed be solved) and a synchronous online examination using Microsoft Teams for practicum (comprising of 12 online OSCE stations). The final grades were evaluated using the same metrics in face-to-face final examinations in 2022 and 2020. A total of 114, 112 and 95 students were recruited for the first-time exams in 2020, 2021 and 2022, respectively. In order to analyze the reliability, histogram and k-mean clustering were employed. The histograms from 2020, 2021 and 2022 showed a striking similarity. However, fewer students failed in 2021 and 2022 (13% and 12.6%, respectively) compared to 2020 (28%), with clinical problem-solving part grades (belonging to theory session) being notably higher in 2021 and 2022. Intriguingly, the MCQ Score results showed the identical patterns. The courses of orthodontics, dental public health, and pediatrics subjects (in the group of prevention and development dentistry) stood out for their exceptional accuracy across both sessions. After examining data gathered over three years, we identified three distinct clusters: the first comprised of scattered average and low scores, the second characterized by high scores but unstable and scattered and the third cluster boasting consistently high and centered scores. According to our study, online and onsite traditional graduation exam results are relatively equivalent, but additional measures are necessary to standardize the final examination and adapt to the new normal trend in dental education.

Searching for New Molecular Targets for Oral Squamous Cell Carcinoma with a View to Clinical Implementation of Precision Medicine.

Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the eighth most common malignancy globally and is characterized by local invasiveness and high nodal metastatic potential. The OSCC incidence is also increasing, and the number of deaths is also rising steadily in Japan. The development of molecular markers to eradicate OSCC is an urgent issue for humankind. The increase in OSCC despite the declining smoking rate may be due to several viral infections through various sexual activities and the involvement of previously unfocused carcinogens, and genetic alterations in individual patients are considered to be more complicated. Given this situation, it is difficult to combat OSCC with conventional radiotherapy and chemotherapy using cell-killing anticancer drugs alone, and the development of precision medicine, which aims to provide tailor-made medicine based on the genetic background of each patient, is gaining attention. In this review article, the current status of the comprehensive search for driver genes and biomarkers in OSCC will be briefly described, and some of the candidates for novel markers of OSCC that were found will be outlined.

SERPINE2 is an oral cancer-promoting factor that induces angiogenesis and lymphangiogenesis.

BACKGROUND: LEM domain containing 1 (LEMD1) is a novel factor involved in the development of oral squamous cell carcinoma (OSCC). We previously performed a microarray analysis and found that serpin peptidase inhibitor, clade E, member 2 (SERPINE2) is an LEMD1-related signal. SERPINE2 is an extracellular serine proteinase inhibitor with secretory capacity. Although SERPINE2 displays tumor-promoting properties in many cancers, some reports indicate that SRPINE2 also has a tumor-suppressing function. Therefore, there are many unclear points about its role in cancer. In this study, we investigated SERPINE2 expression in OSCC. METHODS: The gene expression and secretion levels of SERPINE2 were examined in 42 frozen specimens of OSCC, and SERPINE2 immunostaining was investigated in 167 cases of OSCC. Furthermore, the effect of SERPINE2 on angiogenesis and lymphangiogenesis was analyzed using OSCC cells and endothelial cells. RESULTS: In the frozen specimens, the gene expression (P < 0.0001) and secretion levels (P < 0.0001) of SERPINE2 were higher in OSCC than in the normal oral mucosa. According to the immunohistochemical analysis, SERPINE2 expression was correlated with the depth of invasion (P = 0.0163), nodal metastasis (P = 0.0085), microvessel density (P < 0.0001), and lymphovessel density (P < 0.0001). Additionally, univariate and multivariate analyses indicated that the SERPINE2 expression level was an independent poor prognostic factor for OSCC. In vitro studies using OSCC cells revealed that SERPINE2 promotes angiogenesis and lymphangiogenesis. CONCLUSION: These results suggest that SRPX2 might be a useful tumor marker for OSCC.

Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO.

PURPOSE: Transport and Golgi organization protein 1 (TANGO) promotes angiogenesis and lymphangiogenesis in oral squamous cell carcinoma (OSCC). To elucidate the underlying mechanisms, this study aims to identify and characterize elements downstream of TANGO that mediate its involvement in OSCC. METHODS: In this study, microarray analysis compared gene expression between control and TANGO-repressed HSC3 cells. Protein expression in 213 OSCC tissue samples was analyzed immunohistochemically. RESULTS: TANGO repression decreased or increased expression of Mucin 20 (MUC20) and small proline-rich protein 1B (SPRR1B), respectively. MUC20 increased the growth and invasiveness of OSCC cells via altered matrix metalloproteinase (MMP)-2 and E-cadherin expression and c-met phosphorylation. MUC20 induced angiogenesis and lymphangiogenesis by activating vascular endothelial growth factors A and C. In well-differentiated OSCC, SPRR1B expression was high (P = 0.0091) and correlated with keratinization markers and promoted proliferation by inducing mitogen-activated protein kinase p38 phosphorylation. MUC20 expression correlated significantly with clinical stage (P = 0.0024), lymph node metastasis (P = 0.0036), and number of blood and lymph vessels (P < 0.0001). MUC20-expressing cases had a significantly worse prognosis than non-expressing cases (P < 0.0001). CONCLUSION: MUC20 and SPRR1B located downstream of TANGO may be useful molecular markers for OSCC.

Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma.

Despite dramatic progress in cancer diagnosis and treatment, the five-year survival rate of oral squamous cell carcinoma (OSCC) is still only about 50%. Thus, the need for elucidating the molecular mechanisms underlying OSCC is urgent. We previously identified the peroxidasin gene (PXDN) as one of several novel genes associated with OSCC. Although the PXDN protein is known to act as a tumor-promoting factor associated with the Warburg effect, its function and role in OSCC are poorly understood. In this study, we investigated the expression, function, and relationship with the Warburg effect of PXDN in OSCC. In immunohistochemical analysis of OSCC specimens, we observed that elevated PXDN expression correlated with lymph node metastasis and a diffuse invasion pattern. High PXDN expression was confirmed as an independent predictor of poor prognosis by multivariate analysis. The PXDN expression level correlated positively with that of pyruvate kinase (PKM2) and heme oxygenase-1 (HMOX1) and with lactate and ATP production. No relationship between PXDN expression and mitochondrial activation was observed, and PXDN expression correlated inversely with reactive oxygen species (ROS) production. These results suggest that PXDN might be a tumor progression factor causing a Warburg-like effect in OSCC.

Sushi Repeat Containing Protein X-linked 2 Is a Downstream Signal of LEM Domain Containing 1 and Acts as a Tumor-Promoting Factor in Oral Squamous Cell Carcinoma.

Because oral squamous cell carcinomas (OSCCs) have a high potential for locoregional invasion and nodal metastasis, early detection and treatment are essential. A LAP2, emerin, MAN1 (LEM) domain containing 1 (LEMD1) is associated with local progression, clinical stage, nodal metastasis, poor prognosis, angiogenesis, and lymphangiogenesis in OSCC. Although LEMD is a cancer-testis antigen, the cancer-related signals related to LEMD1 remain unknown. In this study, we used a microarray analysis of OSCC cells to identify sushi repeat containing protein X-linked 2 (SRPX2) as a LEMD1-related downstream signal. LEMD1 expression was correlated with lymph node metastasis of OSCC according to the immunohistochemistry analysis. Furthermore, patients expressing SRPX2 had a significantly worse prognosis than those without SRPX2 expression. The concentration of SRPX2 in OSCC was positively correlated with the concentrations of LEMD1, urokinase plasminogen activator receptor (uPAR), and hepatocyte growth factor (HGF). In OSCC cells, SRPX2 secretion levels were elevated by interactions with uPAR and HGF. We also found that SRPX2 promotes endothelial cell proliferation and adhesion between endothelial cells and OSCC cells. These results suggest that SRPX2 might be a useful tumor marker for OSCC.

Mast cell chymase promotes angiogenesis and lymphangiogenesis mediated by activation of melanoma inhibitory activity gene family members in oral squamous cell carcinoma.

Mast cells (MCs) are present in the tumor stroma, and MCs that express the mast cell­specific proteases tryptase and chymase (MCTC) exhibit several tumor­related functions. It was previously reported that melanoma inhibitory activity (MIA) gene family members, including MIA, MIA2, and transport and Golgi organization protein 1 (TANGO), possess oncogenic functions in oral squamous cell carcinoma (OSCC). However, the relationships between MCTC, and clinicopathological characteristics and activation of the MIA gene family in OSCC remain unknown. In the present study, the functional roles of MCTC in patients with OSCC were investigated using immunohistochemistry and reverse transcription­quantitative PCR. In addition, the effects of extracellular chymase on oral cancer cells were examined. In patients with OSCC, MCTC density was significantly affected by tumor progression and nodal metastasis, and was correlated with vessel density. MCTC density was also correlated with MIA and MIA2 expression. In OSCC cells, extracellular chymase promoted the secretion of vascular endothelial growth factor family proteins, and the transmigration and adhesion of HSC3 cells to endothelial cells; knockdown of MIA, MIA2 and TANGO attenuated these effects. The present findings indicated that MCTC act as tumor­progressive factors in OSCC via the activation and secretion of MIA and MIA2, and the induction of angiogenesis and lymphangiogenesis.

The Oncogenic Activity of miR-29b-1-5p Induces the Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma.

BACKGROUND: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. METHODS: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. RESULTS: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. CONCLUSIONS: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells.

Non-SMC Condensin I Complex Subunit H (NCAPH) Is Associated with Lymphangiogenesis and Drug Resistance in Oral Squamous Cell Carcinoma.

BACKGROUND: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common malignancy. OSCC has strong invasive ability, and its malignant potential is closely associated with local expansion and lymph node metastasis. Furthermore, local or nodal recurrence worsens OSCC prognosis. In our previous cDNA microarray analysis, non-structural maintenance of chromosome (SMC) condensin I complex subunit H (NCAPH) was identified as an upregulated gene in recurrent OSCC. Although NCAPH has several functions in tumors, its role in OSCC is unknown. METHODS: In this study, we examined NCAPH expression in OSCC and performed a functional analysis of human OSCC cells. RESULTS: NCAPH expression was higher in OSCC than in normal oral mucosa. In immunohistochemistry using 142 OSCC specimens, the immunostaining of NCAPH was strongly associated with nodal metastasis and lymphatic infiltration. In multivariate analysis using the Cox proportional hazards model, NCAPH expression was an independent poor prognostic indicator for OSCC. Moreover, NCAPH promoted the migration and adhesion of endothelial cells to OSCC cells and promoted the resistance to platinum anticancer drugs. CONCLUSIONS: Our present findings suggest that NCAPH is a novel diagnostic and therapeutic target in OSCC.

The Multifarious Functions of Pyruvate Kinase M2 in Oral Cancer Cells.

Head and neck cancers, including oral squamous cell carcinoma (OSCC), are the sixth most common malignancies worldwide. OSCC frequently leads to oral dysfunction, which worsens a patient's quality of life. Moreover, its prognosis remains poor. Unlike normal cells, tumor cells preferentially metabolize glucose by aerobic glycolysis. Pyruvate kinase (PK) catalyzes the final step in glycolysis, and the transition from PKM1 to PKM2 is observed in many cancer cells. However, little is known about PKM expression and function in OSCC. In this study, we investigated the expression of PKM in OSCC specimens and performed a functional analysis of human OSCC cells. We found that the PKM2/PKM1 ratio was higher in OSCC cells than in adjacent normal mucosal cells and in samples obtained from dysplasia patients. Furthermore, PKM2 expression was strongly correlated with OSCC tumor progression on immunohistochemistry. PKM2 expression was higher during cell growth, invasion, and apoptosis in HSC3 cells, which show a high energy flow and whose metabolism depends on aerobic glycolysis and oxidative phosphorylation. PKM2 expression was also associated with the production of reactive oxygen species (ROS) and integration of glutamine into lactate. Our results suggested that PKM2 has a variety of tumor progressive functions in OSCC cells.

Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma.

Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC's molecular mechanism is imperative for early detection and treatment, improving patient survival. Based on broadly accepted notions, OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens. In 2011, research revealed 10 key alterations fundamental to cancer cell development: sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, activating invasion and metastasis, tumor-promoting inflammation, enabling replicative immortality, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating energetics. This review describes molecular pathological findings on conventional and novel hallmarks of OSCC prognostic factors. In addition, the review summarizes the functions and roles of several molecules as novel OSCC prognosticators.

Downregulation of DHRS9 is associated with poor prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) has a high potential for local invasion and nodal metastasis. Therefore, early detection and elucidation of the detailed molecular mechanisms underlying OSCC are essential. Dehydrogenase/reductase member 9 (DHRS9) is downregulated in recurrent OSCC. Although DHRS9 is reported to act as a tumour suppressor in several malignancies, its expression in OSCC cells is unknown. In this study, we examined DHRS9 expression immunohistochemically in specimens from a sample of 98 OSCC patients. Reduced DHRS9 expression was observed in 68 of 98 patients (69.4%) with OSCC. A significant association was found between low DHRS9 expression and local progression (T factor) (p = 0.0135). Furthermore, patients with low DHRS9 expression had a significantly poorer prognosis than those with high DHRS9 expression (p = 0.0443). In multivariate analysis using the Cox proportional hazards model, decreased DHRS9 expression strongly correlated with worse prognosis. The study findings suggest that DHRS9 might be a useful diagnostic and prognostic marker for OSCC.

The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer.

Oral squamous cell carcinoma has a high potential for locoregional invasion and nodal metastasis. Consequently, early detection of such malignancies is of immense importance. The melanoma inhibitory activity (MIA) gene family comprises MIA, MIA2, transport and Golgi organization protein 1 (TANGO), and otoraplin (OTOR). These members of the MIA gene family have a highly conserved Src homology 3 (SH3)-like structure. Although the molecules of this family share 34-45% amino acid homology and 47-59% cDNA sequence homology, those members, excluding OTOR, play different tumor-associated functions. MIA has a pivotal role in the progression and metastasis of melanoma; MIA2 and TANGO have been suggested to possess tumor-suppressive functions; and OTOR is uniquely expressed in cochlea of the inner ear. Therefore, the definite functions of the MIA gene family in cancer cells remain unclear. Since the members of the MIA gene family are secreted proteins, these molecules might be useful tumor markers that can be detected in the body fluids, including serum and saliva. In this review, we described the molecular biological functions of the MIA gene family in oral cancer.

Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma.

Malic enzyme 1 (ME1) is a multifunctional protein involved in glycolysis, the citric acid cycle, NADPH production, glutamine metabolism, and lipogenesis. It is overexpressed in various cancers. We examined the expression of ME1 in 119 oral squamous cell carcinomas (OSCCs) using immunohistochemistry. Malic enzyme 1 expression was moderate to strong in 57 (48%) OSCCs and correlated with pT, pN, clinical stage, and histological grade. In 37 cases with prognostic evaluation, moderate to strong ME1 expression indicated a worse prognosis than did weak ME1 expression. Malic enzyme 1 knockdown or inactivation by lanthanide inhibited cell proliferation and motility and suppressed the epithelial-mesenchymal transition in HSC3 human OSCC cells. Knockdown of ME1 also shifted energy metabolism from aerobic glycolysis and lactate fermentation to mitochondrial oxidative phosphorylation, and the redox status from reductive to oxidative. In a mouse tumor model, lanthanide suppressed tumor growth and increased survival time. These findings reveal that ME1 is a valid target for molecular therapy in OSCC.

NIPA-like domain containing 1 is a novel tumor-promoting factor in oral squamous cell carcinoma.

PURPOSE: In our previous global gene expression analysis, we identified NIPA-like domain containing 1 (NIPAL1), which encodes a magnesium transporter, as one of the most overexpressed genes in recurrent oral squamous cell carcinoma (OSCC). Although has been NIPAL1 linked with gout pathogenesis, little is known about its expression and function in human malignancies. METHODS: In this study, we examined NIPAL1 expression in 192 cases of OSCC by immunohistochemistry and performed a functional analysis of human OSCC cells. RESULTS: NIPAL1 immunostaining was observed in 39 of 192 OSCC patients (20.3%). NIPAL1 expression correlated significantly with cancer cell intravsation (P = 0.0062), as well as with poorer disease-free survival in a Kaplan-Meier analysis (P < 0.0001). Moreover, a multivariate Cox proportional hazards model analysis revealed that NIPAL1 expression was an independent predictor of disease-free survival in OSCC (P < 0.0001). In a functional analysis, NIPAL1 regulated the growth and adhesion of OSCC tumor cells and endothelial cells. CONCLUSIONS: Our findings suggest that NIPAL1 might be a novel factor promoting OSCC tumorigenesis, as well as a useful molecular marker of OSCC.

Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and poor prognosis in oral squamous cell carcinoma.

AIMS: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear. METHODS: In this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC. RESULTS: High cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001). CONCLUSIONS: These results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC.

Pancreatic adenocarcinoma up-regulated factor has oncogenic functions in oral squamous cell carcinoma.

AIMS: Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel secretory protein which promotes tumour progression, metastasis and poor prognosis in pancreatic, cervical and colorectal carcinoma. It is also associated with gemcitabine resistance in pancreatic cancer cells. However, the expression and function of PAUF in oral squamous cell carcinoma (OSCC) remain unknown. METHODS AND RESULTS: We performed an immunohistochemical analysis of PAUF in 222 clinicopathologically characterized cases of OSCC. We also investigated the growth, invasion, apoptosis induction and cisplatin resistance of OSCC cells under PAUF knockdown treatment. PAUF was localized in normal salivary glands. In OSCC, immunostaining for PAUF was found in 52 of 222 patients (23.4%), and correlated with nodal metastasis (P < 0.0001) and poor prognosis (P < 0.0001). Multivariate analysis using the Cox proportional hazards model identified that PAUF expression was an independent predictor of disease-free survival in OSCC (P < 0.0001). The down-regulation of PAUF in OSCC cells suppressed cell growth and invasion and induced apoptosis and cisplatin sensitivity. CONCLUSIONS: Our results suggest that PAUF has tumour-promoting functions in OSCC. It may thus be a useful diagnostic and therapeutic marker for OSCC.

LEM domain containing 1 promotes oral squamous cell carcinoma invasion and endothelial transmigration.

BACKGROUND: Oral squamous cell carcinomas have high potential for locoregional invasion and nodal metastasis. Thus, early detection and elucidation of detailed molecular mechanisms of OSCCs are important. Roles of LEM domain containing 1 (LEMD1), a novel cancer-testis antigen, in OSCCs are unclear. METHODS: We performed immunohistochemical analysis of LEMD1 in 289 OSCC patients and examined functions of LEMD1 in these carcinomas. RESULTS: Immunohistochemical analysis showed that 101 patients were positive for LEMD1. LEM domain containing 1 expression levels in OSCCs significantly correlated with tumour progression (T factor and clinical stage), nodal metastasis, and poor prognosis. LEM domain containing 1 expression was an independent predictor of disease-free survival in OSCC patients. In OSCCs, LEMD1 knockdown suppressed cancer cell invasion. Moreover, downregulation of LEMD1 expression inhibited adhesion and transmigration of OSCCs and vascular or lymphatic vascular endothelial cells. CONCLUSIONS: Our findings suggest that LEMD1 is a novel tumour progressive factor and may be a useful diagnostic and therapeutic target in OSCCs.

NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.