Oral Cancer


Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Smoking
  • MicroRNAs
  • Disease Progression
  • Single Nucleotide Polymorphism
  • TWIST1
  • Racemases and Epimerases
  • Reproducibility of Results
  • Public Health
  • Sialoglycoproteins
  • Risk Factors
  • Immunohistochemistry
  • DNA Methylation
  • MMP2
  • Research Design
  • Transcription Factors
  • NAT2
  • Research Personnel
  • Oligoribonucleotides
  • BCL2
  • RNA, Untranslated
  • Case-Control Studies
  • CDK2AP1
  • Down-Regulation
  • Squamous Cell Carcinoma
  • Promoter Regions
  • Biomarkers, Tumor
  • ALDH2
  • S100A7
  • Cell Movement
  • Transfection
  • FAT1
  • Staging
  • IL6
  • Thyrotropin-Releasing Hormone
  • Wnt Signaling Pathway
  • Wound Healing
  • ABCG2
  • NTRK2
  • Genetic Predisposition
  • Tongue Neoplasms
  • Apoptosis
  • Cell Proliferation
  • Cancer Gene Expression Regulation
  • Lymphatic Metastasis
  • Saliva
  • Long Noncoding RNA
  • GSTT1
  • Salivary Gland Cancer
  • Oral Cavity Cancer
  • GSTM1
  • THBS2
  • Gene Expression Profiling
  • Tumor Microenvironment
Tag cloud generated 29 August, 2019 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (55)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

NODAL 10q22.1 HTX5 -NODAL and Oral Cavity Cancer
GSTM1 1p13.3 MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b -GSTM1 and Oral Cavity Cancer
MMP2 16q12.2 CLG4, MONA, CLG4A, MMP-2, TBE-1, MMP-II -MMP2 and Oral Cancer
GSTT1 22q11.23 -GSTT1 and Oral Cavity Cancer
BAX 19q13.33 BCL2L4 -BAX and Oral Cavity Cancer
CA9 9p13.3 MN, CAIX -CA9 and Oral Cavity Cancer
BCL2 18q21.33 Bcl-2, PPP1R50 -BCL2 and Oral Cavity Cancer
TWIST1 7p21.1 CRS, CSO, SCS, ACS3, CRS1, BPES2, BPES3, TWIST, bHLHa38 -TWIST1 and Oral Squamous Cell Carcinoma
NAT2 8p22 AAC2, PNAT, NAT-2 -NAT2 and Oral Cancer
PDPN 1p36.21 T1A, GP36, GP40, Gp38, OTS8, T1A2, TI1A, T1A-2, AGGRUS, HT1A-1, PA2.26 -PDPN and Oral Cavity Cancer
ALDH2 12q24.12 ALDM, ALDHI, ALDH-E2 -ALDH2 and Oral Cavity Cancer
ABCG2 4q22.1 MRX, MXR, ABCP, BCRP, BMDP, MXR1, ABC15, BCRP1, CD338, GOUT1, MXR-1, CDw338, UAQTL1, EST157481 -ABCG2 and Oral Cavity Cancer
CTTN 11q13.3 EMS1 -CTTN and Oral Cavity Cancer
GSTM3 1p13.3 GST5, GSTB, GTM3, GSTM3-3 -GSTM3 and Oral Cavity Cancer
MARCO 2q14.2 SCARA2 -MARCO and Oral Cavity Cancer
FGF4 11q13.3 HST, KFGF, HST-1, HSTF1, K-FGF, HBGF-4 -FGF4 and Oral Cavity Cancer
LAMC2 1q25.3 B2T, CSF, EBR2, BM600, EBR2A, LAMB2T, LAMNB2 -LAMC2 and Oral Cavity Cancer
EDNRB 13q22.3 ETB, ET-B, ETB1, ETBR, ETRB, HSCR, WS4A, ABCDS, ET-BR, HSCR2 -EDNRB and Oral Cavity Cancer
ADH1C 4q23 ADH3 -ADH1C and Oral Cavity Cancer
S100A7 1q21.3 PSOR1, S100A7c -S100A7 and Oral Cavity Cancer
CDK2AP1 12q24.31 DOC1, ST19, DORC1, doc-1, p12DOC-1 -CDK2AP1 and Oral Cavity Cancer
AIDA 1q41 C1orf80 -AIDA and Oral Cavity Cancer
SERPINE1 7q22.1 PAI, PAI1, PAI-1, PLANH1 -SERPINE1 and Oral Cavity Cancer
MMP10 11q22.2 SL-2, STMY2 -MMP10 and Oral Cavity Cancer
WISP1 8q24.22 CCN4, WISP1c, WISP1i, WISP1tc -WISP1 and Oral Cavity Cancer
FAT1 4q35.2 FAT, ME5, CDHF7, CDHR8, hFat1 -FAT1 and Oral Cavity Cancer
RPS6 9p22.1 S6 -RPS6 and Oral Cavity Cancer
NTRK2 9q21.33 TRKB, trk-B, GP145-TrkB -NTRK2 and Oral Cavity Cancer
IL6 7p15.3 CDF, HGF, HSF, BSF2, IL-6, BSF-2, IFNB2, IFN-beta-2 -IL6 and Oral Cavity Cancer
SLPI 20q13.12 ALP, MPI, ALK1, BLPI, HUSI, WAP4, WFDC4, HUSI-I -SLPI and Oral Cavity Cancer
THBS2 6q27 TSP2 -THBS2 and Oral Cavity Cancer
ITGB4 17q25.1 CD104, GP150 -ITGB4 and Oral Cavity Cancer
KIAA1524 3q13.13 p90, CIP2A -KIAA1524 and Oral Cavity Cancer
ENDOU 12q13.1 P11, PP11, PRSS26 -ENDOU and Oral Cavity Cancer
CSMD1 8p23.2 PPP1R24 -CSMD1 and Oral Cavity Cancer
IMP3 15q24.2 BRMS2, MRPS4, C15orf12 -IMP3 and Oral Cavity Cancer
PRRX1 1q24.2 PMX1, PRX1, AGOTC, PHOX1, PRX-1 -PRRX1 and Oral Cavity Cancer
DEC1 9q33.1 CTS9 -DEC1 and Oral Cavity Cancer
WNT11 11q13.5 HWNT11 -WNT11 and Oral Cavity Cancer
MALL 2q13 BENE -MALL and Oral Cavity Cancer
FGF19 11q13.3 -FGF19 and Oral Cavity Cancer
ING5 2q37.3 p28ING5 -ING5 and Oral Cavity Cancer
BCL2A1 15q25.1 GRS, ACC1, ACC2, BFL1, ACC-1, ACC-2, HBPA1, BCL2L5 -BCL2A1 and Oral Cavity Cancer
HOXC13 12q13.13 HOX3, ECTD9, HOX3G -HOXC13 and Oral Cavity Cancer
BDNF 11p14.1 ANON2, BULN2 -BDNF and Oral Cavity Cancer
TMC8 17q25.3 EV2, EVER2, EVIN2 -TMC8 and Oral Cavity Cancer
RXRB 6p21.3 NR2B2, DAUDI6, RCoR-1, H-2RIIBP -RXRB and Oral Cavity Cancer
GHRH 20q11.23 GRF, INN, GHRF -GHRH and Oral Cavity Cancer
DDR2 1q23.3 TKT, WRCN, MIG20a, NTRKR3, TYRO10 -DDR2 and Oral Cavity Cancer
ANXA8 10q11.22 ANX8, CH17-360D5.2 -ANXA8 and Oral Cavity Cancer
MIRLET7I 12q14.1 LET7I, let-7i, MIRNLET7I, hsa-let-7i -None and Oral Cavity Cancer
SPRR2B 1q21.3 -SPRR2B and Oral Cavity Cancer
TNFRSF8 1p36.22 CD30, Ki-1, D1S166E -TNFRSF8 and Oral Cavity Cancer
TMC6 17q25.3 EV1, EVER1, EVIN1, LAK-4P -TMC6 and Oral Cavity Cancer
CFLAR 2q33-q34 CASH, FLIP, MRIT, CLARP, FLAME, Casper, FLAME1, c-FLIP, FLAME-1, I-FLICE, c-FLIPL, c-FLIPR, c-FLIPS, CASP8AP1 -CFLAR and Oral Cavity Cancer

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications

Tomasovic-Loncaric C, Fucic A, Andabak A, et al.
Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk.
Anticancer Res. 2019; 39(8):4285-4289 [PubMed] Related Publications
BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC.
PATIENTS AND METHODS: Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry.
RESULTS: More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients.
CONCLUSION: More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.

Imai A, Mochizuki D, Misawa Y, et al.
DNA Cell Biol. 2019; 38(7):678-687 [PubMed] Related Publications
Staging and pathological grading systems are convenient, but imperfect predictors of recurrence of head and neck squamous cell carcinoma. Therefore, to identify potential alternative prognostic markers, we investigated the methylation status of the promoter of Sal-like protein 2 (

Huang SJ, Tseng YK, Lo YH, et al.
Association of
Anticancer Res. 2019; 39(6):2891-2902 [PubMed] Related Publications
BACKGROUND/AIM: Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC.
MATERIALS AND METHODS: This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method.
RESULTS: Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype.
CONCLUSION: We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect.

Bao XD, Lin LS, Chen F, et al.
[Association of single nucleotide polymorphisms of
Zhonghua Yu Fang Yi Xue Za Zhi. 2019; 53(5):480-485 [PubMed] Related Publications

Xiao Y, Li H, Yang LL, et al.
The Expression Patterns and Associated Clinical Parameters of Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 and Transmembrane and Immunoglobulin Domain Containing 2 in Oral Squamous Cell Carcinoma.
Dis Markers. 2019; 2019:5421985 [PubMed] Free Access to Full Article Related Publications
Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) and transmembrane and immunoglobulin domain containing 2 (TMIGD2) are new immune checkpoint molecules of the B7:CD28 family; however, little research has been performed on these immune checkpoint molecules. In this study, we used oral squamous cells carcinoma (OSCC) tissue microarrays and immunohistochemistry methods to investigate the expression patterns of HHLA2 and TMIGD2 in OSCC. After comparing the HHLA2 and TMIGD2 expression levels in OSCC, dysplasia, and mucosa, we found increased HHLA2 expression in OSCC and dysplasia, while the TMIGD2 expression was decreased in OSCC and dysplasia. Using the Kaplan-Meier method and log-rank test, we found that higher HHLA2 or TMIGD2 expression levels in OSCC indicate poor prognosis. Furthermore, two-tailed Pearson's statistical analysis revealed that the HHLA2 expression levels in OSCC, dysplasia, and mucosa were positively correlated with the T cell immunoglobulin and mucin-domain containing-3 (TIM3), lymphocyte-activation gene 3 (LAG3), B7 homolog 3 protein (B7-H3), B7 homolog 4 protein (B7H4), and V-domain Ig suppressor of T cell activation (VISTA) levels, while the TMIGD2 expression levels in OSCC, dysplasia, and mucosa were inversely correlated with the TIM3, LAG3, and B7H3 levels. Our current study demonstrates that HHLA2 may serve as an immune target for OSCC therapy and that the TMIGD2 expression level in OSCC could forecast patient prognosis.

Su W, Wang Y, Wang F, et al.
Hsa_circ_0005379 regulates malignant behavior of oral squamous cell carcinoma through the EGFR pathway.
BMC Cancer. 2019; 19(1):400 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy with a high incidence worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a vital role in modulating tumor development. However, the mechanism of circRNA action in human OSCC remains largely unknown.
METHODS: By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The effect of circRNA hsa_circ_0005379 on OSCC tissues and cell lines was monitored by qRT-PCR, Transwell assay, flow cytometry, and western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival.
RESULTS: We found that circRNA hsa_circ_0005379 expression is significantly lower in OSCC tissue compared to paired non-cancerous matched tissue and is associated with tumor size and differentiation. Overexpression of hsa_circ_0005379 effectively inhibits migration, invasion, and proliferation of OSCC cells in vitro and suppresses OSCC growth in nude mice in vivo. Mechanistic studies revealed that hsa_circ_0005379 may be involved in the regulation of the epidermal growth factor receptor (EGFR) pathway. Furthermore, we found that high expression of hsa_circ_0005379 could significantly enhance the sensitivity of OSCC to the cetuximab drug.
CONCLUSIONS: Our findings provide evidence that hsa_circ_0005379 regulates OSCC malignancy and may be a new therapeutic target for OSCC treatment.

Li JY, Huang WX, Zhou X, et al.
Numb inhibits epithelial-mesenchymal transition via RBP-Jκ-dependent Notch1/PTEN/FAK signaling pathway in tongue cancer.
BMC Cancer. 2019; 19(1):391 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Oral cancer has been estimated as the sixth most frequent solid cancer all over the world, in which tongue squamous cell carcinoma (TSCC) is the most common type of oral cancers. However, the mechanism of TSCC metastasizing to lymph node and distant sites has not been completely understood.
METHODS: In this study, RT-qPCR method was used to detect the mRNA level of Numb, PTEN and Notch1 genes, as well as EMT-associated genes. Western blot assay was utilized to detect protein level of these genes. In addition, we determined cell proliferation by MTT assay and employed transwell invasion assay and wound healing assay to probe the abilities of invasion and migration, respectively. To investigate the role of PTEN, its inhibitor VO-Ohpic trihydrate was used to treat SCC-4 and CAL27 cells.
RESULTS: We found that Numb expression was downregulated in SCC-9 and CAL-27 cells compared to NHOK cells. Instead, Notch1 level in SCC-9 and CAL-27 cells were higher than that in NHOK cells. Furthermore, the results showed that Numb overexpression significantly suppressed proliferation, migration and invasion of SCC-9 and CAL-27 cells via regulating Notch1 signaling and EMT-related genes expression. By contrast, we observed that RBP-Jκ knockdown had an inhibitory role in proliferation, migration and invasion of SCC-9 and CAL-27 cells. In cells with Numb overexpression or RBP-Jκ knockdown, p-FAK and EMT-related genes were remarkably regulated.
CONCLUSIONS: Our findings provide new mechanism of understanding the metastasis of TSCC and help develop therapeutic strategies for treating tongue cancer.

Cervino G, Fiorillo L, Herford AS, et al.
Molecular Biomarkers Related to Oral Carcinoma: Clinical Trial Outcome Evaluation in a Literature Review.
Dis Markers. 2019; 2019:8040361 [PubMed] Free Access to Full Article Related Publications
Backgrounds: The objective of the present research was to systematically revise the international literature about the genetic biomarkers related to oral cancer (OC) evaluating the recent findings in clinical studies.
Methods: A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. The authors conducted the search of articles in the English language published from 2008 to 2018. The present systematic review included only papers with significant results about correlation between wound healing, genetic alteration, and OC. Prognostic capacity of genetic markers was not evaluated in vivo.
Results: The first analysis with filters recorded about 1884 published papers. Beyond reading and consideration of suitability, only 20 and then 8 papers, with case report exclusion, were recorded for the revision.
Conclusion: All the researches recorded the proteomic and genetic alterations in OC human biopsy cells. The gene modification level in the different studies, compared with samples of healthy tissues, has always been statistically significant, but it is not possible to associate publications with each other because each job is based on the measurement of different biomarkers and gene targets. Further investigations should be required in order to state scientific evidence about a clear advantage of using these biomarkers for diagnostic purpose.

Chen WC, Li QL, Pan Q, et al.
Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling.
J Exp Clin Cancer Res. 2019; 38(1):167 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Xenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized.
METHODS: Real-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay.
RESULTS: Herein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens.
CONCLUSIONS: These findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.

Shi J, Liu Z, Xu Q
Tumor necrosis factor receptor-associated factor 6 contributes to malignant behavior of human cancers through promoting AKT ubiquitination and phosphorylation.
Cancer Sci. 2019; 110(6):1909-1920 [PubMed] Free Access to Full Article Related Publications
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been found to be involved in carcinogenesis in multiple cancers. However, the precise role of TRAF6 in cancer has not been extensively investigated and remains largely unknown. In this study, we aimed to investigate the biological function of TRAF6 and its underlying molecular mechanisms in cancer. A positive correlation between poor tumor differentiation and TRAF6 expression status was observed in both oral cancer and breast cancer. Overexpression of TRAF6 promoted proliferation, migration, and G

Chamorro Petronacci CM, Pérez-Sayáns M, Padín Iruegas ME, et al.
miRNAs expression of oral squamous cell carcinoma patients: Validation of two putative biomarkers.
Medicine (Baltimore). 2019; 98(13):e14922 [PubMed] Free Access to Full Article Related Publications
microRNA expression patterns have provided new directions in the search of biomarkers with prognostic value and even in the search of novel therapeutic targets for several neoplasms. Specifically, miRNAs profiling in oral squamous cell carcinoma (OSCC) represents a web of intrigue in the study of oral carcinogenesis. The objective of the present study was twofold:The first study phase comprised case-control groups: A) 8 OSCC-affected patients and 8 healthy controls. Microarray technology (Affymetrix miRNA Array Plate 4.1) was used for miRNAs expression profile. Deregulated miRNAs were studied using Diana Tools miRPath 3.0 to associate miRNA targets with molecular pathways via Kyoto Encyclopedia of Genes and Genomes (KEGG). In a second phase, 2 miRNAs chosen for the subsequent RT-qPCR validation were studied in a second OSSC cohort (n = 8).Microarray analysis identified 80 deregulated miRNAs (35 over-expressed and 45 under-expressed). Two miRNAs (miR-497-5p and miR-4417) were chosen for further validation via RT-qPCR. Prognostic analysis did not ascertain relevant relation between miR-497-5p or miR-4417 expression and clinical or pathological parameters, except high miR-4417 in the case of nodular affectation (P = .035) and diminished miR-497-5p radiotherapy-treated patients (P = .05). KEGG analysis revealed that deregulated miRNAs were implicated in several biological pathways such as Proteoglycans in cancer.Our data suggest an altered miRNAs profiling in OSCC-affected patients. We have verified the altered expression of miR-497-5p and miR-4417 in OSCC samples and related the deregulated miRNAs with the 'proteoglycans in cancer' pathway. Further longitudinal studies with large samples are warranted to confirm the present findings.

Goud EVSS, Malleedi S, Ramanathan A, et al.
Association of Interleukin-10 Genotypes and Oral Cancer Susceptibility in Selected Malaysian Population: A Case- Control Study
Asian Pac J Cancer Prev. 2019; 20(3):935-941 [PubMed] Related Publications
Background: Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10 A1082G gene polymorphism was correlated. Methodology: 41 oral squamous cell carcinoma (OSCC) cases and 48 healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square test and Fisher’s Exact test were used in statistical analysis. Results: AG genotypes were present in 81.3% and 86.0% of healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival. The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion. Conclusion: This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence to support the lack of association of IL10 A1082G polymorphism in oral cancer.

Jiang L, Lv L, Liu X, et al.
MiR-223 promotes oral squamous cell carcinoma proliferation and migration by regulating FBXW7.
Cancer Biomark. 2019; 24(3):325-334 [PubMed] Free Access to Full Article Related Publications
Abnormally expressed microRNAs (miRNAs) contribute widely to human cancer, including oral squamous cell carcinoma (OSCC), by regulating their downstream targets. MiR-223 has been proved to be up-regulated in both gastric cancer and ovarian cancer. However, the effect of miR-223 on OSCC is still unclear. Here, we showed that miR-223 was over-expressed in OSCC tissues using qRT-PCR. Next, we investigated the biological mechanism of miR-223 in OSCC. The results demonstrated that miR-223 facilitated the cell proliferation and migration of OSCC using MTT assay and Transwell assay. Furthermore, we stated that the FBXW7 expression was decreased in OSCC and re-expression of FBXW7 inhibited the proliferation and migration of OSCC. In addition, FBXW7 mimic inversed the promotion effect of miR-223 in regulating of OSCC cells. In short, miR-223 promoted OSCC cell proliferation and migration by downregulating FBXW7, which provided a novel therapeutic strategy for OSCC.

Shi B, Ma C, Liu G, Guo Y
MiR-106a directly targets LIMK1 to inhibit proliferation and EMT of oral carcinoma cells.
Cell Mol Biol Lett. 2019; 24:1 [PubMed] Free Access to Full Article Related Publications
Background: LIM kinase 1 (LIMK1) expression levels are closely associated with microRNA (miRNA) processing. Higher levels of LIMK1 are reported during the progression of many cancers. Our study explored the interaction between LIMK1 and miR-106a in oral squamous cell carcinoma (OSCC).
Methods: Quantitative RT-PCR was performed to detect the levels of LIMK1 and miR-106a in OSCC tissues and cell lines. The rates of cell proliferation and epithelial-mesenchymal transition (EMT) were assessed to determine the biological functions of miR-106a and LIMK1 in OSCC cells. The mRNA and protein levels of LIMK1 were measured using quantitative RT-PCR and western blotting. Luciferase assays were performed to validate LIMK1 as an miR-106a target in OSCC cells.
Results: We found that the level of miR-106a significantly decreased and the expression of LIMK1 significantly increased in OSCC tissues and cell lines. There was a close association between these changes. Knockdown of LIMK1 significantly inhibited the proliferation and EMT of OSCC cells. The bioinformatics analysis predicted that LIMK1 is a potential target gene of miR-106a and the luciferase reporter assay confirmed that miR-106a could directly target LIMK1. Introduction of miR-106a to OSCC cells had similar effects to LIMK1 silencing. Overexpression of LIMK1 in OSCC cells partially reversed the inhibitory effects of the miR-106a mimic.
Conclusion: MiR-106a inhibited the cell proliferation and EMT of OSCC cells by directly decreasing LIMK1 expression.

Yang Z, Liu Z, Meng L, Ma S
Identification of key pathways regulated by a set of competitive long non-coding RNAs in oral squamous cell carcinoma.
J Int Med Res. 2019; 47(4):1758-1765 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: The aim of this study was to identify important pathways regulated by a set of long non-coding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC).
METHODS: A lncRNA-mediated competitive endogenous RNA network (LMCN) was constructed using information on microRNA (miRNA)-mRNA interactions and lncRNA-miRNA intersections from the E-GEOD-37991 transcription profiling data in the ArrayExpress database. A random walk with restart ranking algorithm was then applied to evaluate the influences of protein-coding genes regulated by competitive lncRNAs. Pathway enrichment scores were calculated based on the propagation scores of protein-coding genes. Finally, permutation tests were used to estimate the significance of the pathways.
RESULTS: We obtained lncRNA-mRNA interactions based on miRNAs common to both miRNA-mRNA interactions and lncRNA-miRNA intersections, and used interactions with a z-score > 0.7 to construct a LMCN. Ten lncRNAs were identified as source nodes in the LMCN, and nine pathways with enrichment scores >0.8, including 'Cell cycle', 'Endocytosis', and 'Pathways in cancer', were significantly enriched by these source nodes.
CONCLUSIONS: Nine significant pathways regulated by a set of competitive lncRNAs were identified in OSCC, which may play important roles in the development of OSCC via the cell cycle and endocytosis.

Muraki Y, Hasegawa T, Takeda D, et al.
Induced Pluripotent Stem Cell-related Genes Correlate With Poor Prognoses of Oral Squamous Cell Carcinoma.
Anticancer Res. 2019; 39(3):1205-1216 [PubMed] Related Publications
BACKGROUND/AIM: We recently investigated the contribution of the iPS-related genes SOX2, OCT4, and Nanog to de-differentiation by assaying for their mRNA levels. Given that mRNA expression does not always correlate with the protein levels, the aim of this study was to retrospectively determine the expression of these four iPS-related factors in human OSCC specimens by immunohistochemistry and examine their association with patient prognosis.
MATERIALS AND METHODS: iPS cell-related gene expression in 89 OSCC patients by tissue microarray, and its correlation with clinicopathological factors, differentiation, metastasis, and poor prognoses were investigated.
RESULTS: No evidence of statistically significant relationships was found between the expression of iPS cell-related genes and clinicopathological parameters. However, our data indicated that KLF4 expression was associated with survival, and poor tumor differentiation. In addition, high expression of KLF4 was an independent poor prognostic factor (p=0.004) for OSCC patients.
CONCLUSION: In preoperative biopsies, higher KLF4 and poor differentiation may be clinically effective predictors for the prognosis of oral cancer.

Rajesh D, Azeem Mohiyuddin SM, Balakrishna S, Kutty AVM
Nicotinic acetylcholine receptor gene polymorphism is not associated with tobacco-related oral squamous cell carcinoma.
Indian J Cancer. 2018 Oct-Dec; 55(4):399-403 [PubMed] Related Publications
BACKGROUND: Nicotinic acetylcholine receptor is implicated in carcinogenesis indirectly through increasing nicotine dependence and directly through its impact on cell-cycle regulation. Functional polymorphism in nicotinic acetylcholine receptor alpha-5 subunit gene (CHRNA5 c.1192G>A; rs16969968) is associated with nicotine dependence and risk of lung cancer.
AIM: The aim of this study was to evaluate the association of CHRNA5 c.1192G>A polymorphism with the risk of oral squamous cell carcinoma (OSCC).
SETTINGS AND DESIGN: This was a rural teaching hospital-based case-control study.
MATERIALS AND METHODS: A total of 100 histopathologically confirmed cases of OSCC patients and 100 age- and gender-matched healthy individuals were genotyped for CHRNA5 c.1192G>A polymorphism by polymerase chain reaction-restriction fragment length polymorphism method. Allele and genotype frequencies among case and control groups were compared by Chi-squared test (Fisher's exact).
RESULTS: The frequency of CHRNA5 c.1192A allele was 22% in OSCC patients and 26% in control individuals. The difference in the distribution of alleles and genotypes between case and control groups was not significant (P > 0.05).
CONCLUSIONS: CHRNA5 c.1192G>A polymorphism is not associated with the risk of developing OSCC.

Chen YJ, Liao YJ, Lin F, et al.
[Shared functional modules for nasopharyngeal and oral squamous cell carcinoma identified by network analysis of transcriptomes].
Yi Chuan. 2019; 41(2):146-157 [PubMed] Related Publications
Although nasopharyngeal carcinoma (NPC) and oral squamous cell carcinoma (OSCC) are highly correlated clinical diseases, the underling molecular mechanisms to link the two diseases remain largely unknown. The aim of this study is to identify the shared functional modules for NPC and OSCC by using large-scale transcriptomic data. Gene expression profile datasets of NPC and OSCC were obtained from the GEO database. A total of 1279 differentially expressed genes (DEGs) of NPC and 1293 DEGs of OSCC were identified by fold change and empirical Bayes method, and 278 DEGs were common to these two diseases. These overlapped genes were translated into a primary network consisting of 1290 nodes (genes) and 1766 edges. The primary network was then decomposed into 15 compacted modules (subnets) with high modularity by Newman's algorithm. Topological analysis of these modules identified a total of 58 hub genes, most of which (e.g., PCNA, CDK1, STAT1, CCL5, and MMP1) have been proved to be associated with NPC and/or OSCC, while the rest (e.g., MELK, NME1, RACGAP1, INHBA, and NID1) might be novel risk genes for the two diseases. Further bioinformatics analysis of KEGG databases revealed that these modules are involved in multiple pathogenic biological pathways for either NPC or OSCC (e.g., p53 signaling pathway, ECM-receptor interaction, focal adhesion, and cell cycle). This study demonstrates that NPC and OSCC have similar molecular bases, and the identified pleiotropic modules may shape the complicated molecular interplays underlying the two clinically correlated diseases.

Nigam K, Sanyal S, Gupta S, et al.
Alteration of the Risk of Oral Pre-Cancer and Cancer in North India Population by CYP1A1 Polymorphism Genotypes and Haplotype
Asian Pac J Cancer Prev. 2019; 20(2):345-354 [PubMed] Related Publications
Background: The aim of this study was to evaluate any association between CYP1A1 (T6235C and C4887A, A4889G) gene polymorphisms and the risk of oral pre-cancer and cancer. Methods: In the present study, 250 patients with oral pre-cancer and/or cancer and 250 healthy controls were genotyped for CYP1A1 T6235C, C4887A and A4889G polymorphisms by the PCR-RFLP method. Results: None of the CYP1A1 polymorphisms were associated with the risk of either oral cancer or pre cancer. Nor were any links with clinical parameters of oral cancer found. However, among the consumers of areca nut/pan masala the TC, CA and AG genotypes respectively for the CYP1A1 T6235C,C4887Aand A4889G polymorphisms were significantly more frequent in controls compared to cases (p values for cases vs. controls of 0.0032, 0.0019 and 0.0009, respectively). Similarly, compared to the haplotype TCA, TAG constituted by CYP1A1 T6235C and C4887A and A4889G was more common in controls (6.88%) than in cases (4.07%). Conclusion: Our results suggest that genotypes regarding CYP1A1 polymorphisms may modulate the risk of oral cancer and pre-cancer among the areca nut/pan masala consumers. The haplotype may also exert an influence in our north Indian population.

Huang WC, Jang TH, Tung SL, et al.
A novel miR-365-3p/EHF/keratin 16 axis promotes oral squamous cell carcinoma metastasis, cancer stemness and drug resistance via enhancing β5-integrin/c-met signaling pathway.
J Exp Clin Cancer Res. 2019; 38(1):89 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Targeting the c-Met signaling pathway has become a therapeutic strategy in multiple types of cancer. We unveiled a novel c-Met regulating mechanism that could be applied as a modality for oral squamous cell carcinoma (OSCC) therapy.
METHODS: Upregulation of keratin 16 (KRT16) was found by comparing isogenic pairs of low and high invasive human OSCC lines via microarray analysis. OSCC cells with ectopic expression or silencing of KRT16 were used to scrutinize functional roles and associated molecular mechanisms.
RESULTS: We observed that high KRT16 expression significantly correlated with poorer pathological differentiation, advanced stages, increased lymph nodes metastasis, and decreased survival rate from several Taiwanese OSCC patient cohorts. We further revealed that miR-365-3p could target ETS homologous factor (EHF), a KRT16 transcription factor, to decrease migration, invasion, metastasis and chemoresistance in OSCC cells via inhibition of KRT16. Under confocal microscopic examination, c-Met was found possibly partially associates with KRT16 through β5-integrin. Colocalization of these three proteins may facilitate c-Met and β5-integrin-mediated signaling in OSCC cells. Depletion of KRT16 led to increased protein degradation of β5-integrin and c-Met through a lysosomal pathway leading to inhibition of their downstream Src/STAT3/FAK/ERK signaling in OSCC cells. Knockdown of KRT16 enhanced chemosensitivity of OSCC towards 5-fluorouracil (5-FU). Various combination of c-Met inhibitor (foretinib), protein tyrosine kinase inhibitor (genistein), β5-integrin antibody, and 5-FU markedly augmented cytotoxic effects in OSCC cells as well as tumor killing effects in vitro and in vivo.
CONCLUSIONS: Our data indicate that targeting a novel miR-365-3p/EHF/KRT16/β5-integrin/c-Met signaling pathway could improve treatment efficacy in OSCC.

Ma Q
MiR-219-5p suppresses cell proliferation and cell cycle progression in esophageal squamous cell carcinoma by targeting CCNA2.
Cell Mol Biol Lett. 2019; 24:4 [PubMed] Free Access to Full Article Related Publications
Background: We investigated the potential regulatory role of miR-219-5p in esophageal squamous cell carcinoma (ESCC) and looked at the underlying mechanisms in ESCC.
Methods: Real-time PCR was used to determine the levels of miR-219-5p in ESCC tissues and cell lines. The effects of miR-219-5p and cyclin A2 (CCNA2) on cell proliferation and cell cycle progression were evaluated using MTT, colony formation and flow cytometry assays with ESCC cell lines EC9706 and TE-9. Bioinformatics techniques and the luciferase reporter assay were applied to validate CCNA2 as the miR-219-5p target in ESCC cells. The mRNA and protein levels of CCNA2 were measured using real-time PCR and western blotting.
Results: MiR-219-5p expression was significantly lower in ESCC tissues and cells than in healthy tissues. Upregulation of miR-219-5p repressed cell proliferation and induced cell cycle arrest at the G2/M phase. CCNA2 was identified and confirmed as a direct downstream target of miR-219-5p and its expression negatively correlated with miR-219-5p profiles in ESCC tissues. Knockdown of CCNA2 potentiated the effects of miR-219-5p on cell proliferation and cell cycle distribution.
Conclusions: Our results demonstrate that miR-219-5p might function as a tumor suppressor by directly targeting CCNA2 expression. It could serve as a new therapeutic target for ESCC.

Jia B, Qiu X, Chu H, et al.
Wnt7a predicts poor prognosis, and contributes to growth and metastasis in tongue squamous cell carcinoma.
Oncol Rep. 2019; 41(3):1749-1758 [PubMed] Related Publications
Regional and distant metastases are the principal reasons underlying the high mortality rate associated with tongue squamous cell carcinoma (TSCC); however, the precise molecular mechanisms involved in tongue tumorigenesis remain unknown. The present study aimed to determine the expression and mechanism of regulation of Wnt7a in the growth and metastasis of TSCC. Wnt7a mRNA and protein expression levels were examined in TSCC tissues using reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining. A loss‑of‑function assay was performed in TSCC cell lines using Wnt7a small interfering RNA or short hairpin RNA, after which, cell proliferation, migration and invasion were analyzed using Cell Counting Kit‑8, tumorigenicity and Transwell assays, respectively. Epithelial‑mesenchymal transition (EMT)‑associated proteins were detected by western blotting. The mRNA and protein expression levels of Wnt7a were significantly upregulated in cancer tissues compared with in the adjacent non‑cancerous tissues. Clinical analysis indicated that Wnt7a expression was associated with T classification, lymph node metastasis and pathological differentiation, and high Wnt7a expression predicted a short recurrence‑free survival for patients with TSCC. Silencing Wnt7a expression suppressed cell proliferation, migration and invasion, and reversed the EMT phenotype in TSCC cell lines. The present study revealed that Wnt7a may be upregulated in TSCC, where it may participate in modulating cell proliferation, migration, invasion and the EMT of TSCC. Therefore, Wnt7a should be considered a novel oncogene, and a potential prognostic and therapeutic target for patients with TSCC.

Wei D, Shen B, Wang W, et al.
MicroRNA‑199a‑5p functions as a tumor suppressor in oral squamous cell carcinoma via targeting the IKKβ/NF‑κB signaling pathway.
Int J Mol Med. 2019; 43(4):1585-1596 [PubMed] Free Access to Full Article Related Publications
MicroRNAs (miRNAs) have been shown to have a significant role in the progression of several types of cancer, including oral squamous cell carcinoma (OSCC). However, the biological function and regulatory mechanisms of miRNAs in OSCC remain to be fully elucidated. The aim of the present study was to investigate the role of miRNAs in OSCC and the relevant mechanism. Using a microarray, it was found that miRNA (miR)‑199a‑5p was one of the most downregulated miRNAs in OSCC tissues. A low expression of miR‑199a‑5p was closely associated with tumor differentiation, lymph node metastasis, tumor‑node‑metastasis stage, and overall survival rate. Functionally, the overexpression of miR‑199a‑5p suppressed cell proliferation, induced G0/G1 cell cycle arrest, and promoted the apoptosis of Tca8113 and SCC‑4 cells. Subsequently, inhibitor of nuclear factor‑κB (NF‑κB) kinase β (IKKβ), an important regulator of NF‑κB activation, was identified as a direct target of miR‑199‑5p. An inverse correlation was found between miR‑199a‑5p and IKKβ in tumor tissues. Further investigations revealed that the overexpression of IKKβ efficiently abrogated the influences caused by the overexpression of miR‑199a‑5p. It was also found that the miR‑199a‑5p‑mediated anticancer effects were dependent on the inhibition of NF‑κB activation. These findings indicate that miR‑199a‑5p functions as a tumor suppressor through regulation of the NF‑κB pathway by targeting IKKβ in OSCC.

Moratin J, Hartmann S, Brands RC, et al.
MicroRNA expression correlates with disease recurrence and overall survival in oral squamous cell carcinoma.
J Craniomaxillofac Surg. 2019; 47(3):523-529 [PubMed] Related Publications
OBJECTIVES: Locoregional disease recurrence and metastatic events are the leading causes of death and the most important prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). A major goal of oncology is the identification of clinical and molecular parameters to evaluate the individual risk of recurrence. MicroRNAs (miRNAs) have been shown to correlate well with tumor size and differentiation. Therefore, they are candidate biomarkers for estimating clinical outcomes.
MATERIALS AND METHODS: In this study, the expression levels of distinct miRNAs extracted from formalin-fixed, paraffin-embedded (FFPE) samples of oral squamous cell carcinoma were compared.
RESULTS: Statistical analysis revealed significant correlations between distinct miRNAs and disease recurrence (miR-99*, miR-194*; p < 0.05) and overall survival (miR-99*; p < 0.05). The results were then validated via data from The Cancer Genome Atlas (TCGA).
CONCLUSIONS: Our data show that miR-99* and miR-194* can possibly serve as biomarkers for clinical outcome in HNSCC. These findings may help to identify high-risk patients, who could profit from a more individualized treatment and follow-up.

Zhao F, Chen CW, Yang WW, et al.
Hsa_circRNA_0059655 plays a role in salivary adenoid cystic carcinoma by functioning as a sponge of miR-338-3p.
Cell Mol Biol (Noisy-le-grand). 2018; 64(15):100-106 [PubMed] Related Publications
Circular RNAs(circRNA) are recently demonstrated to have a close relationship with tumors.To investigate the role of circular RNA in the pathogenesis of salivary adenoid cystic carcinoma(SACC), ten SACC tissues and paired normal submandibular gland(SMG) tissues were collected as the tumor group and the control group. Total RNA was extracted and then measured using ceRNA microarray (including mRNA, lncRNA, and circRNA) and miRNA microarray. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis were performed in order to investigate the function of the differential expressing genes. The ceRNA regulatory network was constructed to find the core circRNAs. Then the role of circRNA on proliferation was examined in the SACC cell line SACC-83 using CCK-8,qRT-PCR and western blotting, and its roles on migration and invasion were examined using wound healing assay and transwell assay. The results of the microarrays showed that 3792 mRNAs, 7649 lncRNAs, 11553 circRNAs, and 132 miRNAs expressed differentially. The ceRNA regulatory network analysis showed that hsa_circ_0059655 and other 14circRNAs derived from PYGB target on several similar genes by miR-338-3p.Among the 15 circRNAs derived from PYGB, hsa_circ_0059655has the most relationships in the ceRNA network. Furthermore, after hsa_circ_0059655 was knocked down in SACC-83 cells, the expression of hsa-miR-338-3p was up-regulated while CCND1was down-regulated. The proliferation, migration, and invasion of SACC-83 cells also decreased after hsa_circ_0059655 knock-downed.Taken together, the circRNAs derived from PYGB may regulate the tumorigenesis and development of SACC through competing with miR-338-3p.

Avci H, Iplik ES, Aydemir L, et al.
Are XPD and XPG gene variants related to the mechanism of oral squamous cell carcinoma?
Cell Mol Biol (Noisy-le-grand). 2018; 64(15):94-99 [PubMed] Related Publications
Oral cavity cancers have anatomically a big part of the body system and include several types of cancer. The aim of the study is to investigate the relation between XPG and XPD gene variants in the DNA repair system and oral squamous cell cancers. A total of 111 patients with a pathologic diagnosis of oral squamous cell carcinoma and a control group of 148 healthy volunteers who presented to Istanbul Faculty of Medicine, Department of Otolaryngology & Head and Neck Surgery and Dentistry Faculty were included in the study. Isolation of DNA was achieved using an Invitrogen Purelink Genomic DNA Kit. XPD alleles of Lys751Gln (rs13181) and XPG Asp1104His (rs17655) loci from genomic DNA samples were reproduced using polymerase chain reaction. A statistically significant difference in XPD genotype distribution between control and patient groups was determined (P=0.019). XPD Lys+ was significantly more common in the patient group than in the control group, and a two-fold increased risk for disease was determined. XPD Gln/Gln+ was significantly more common in the control group than in the patient group, and a two-fold decrease in risk for disease was determined (P=0.045). In the other region of the study, there was no statistically significant difference in terms of disease development between XPG genotypes. In conclusion, Lys751Gln polymorphism in the XPD gene could play a role in oral squamous cell development. It is important to increase the numbers of subjects in patient groups and healthy controls in studies to increase the possibility of determining XPD's potential as a molecular risk factor.

Wong K, van der Weyden L, Schott CR, et al.
Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma.
Nat Commun. 2019; 10(1):353 [PubMed] Free Access to Full Article Related Publications
Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identifies several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.

Haller F, Bieg M, Will R, et al.
Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands.
Nat Commun. 2019; 10(1):368 [PubMed] Free Access to Full Article Related Publications
The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. The secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related phosphoproteins of which some are specifically expressed at high levels in the salivary glands and constitute major components of saliva. Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. We show that NR4A3 is specifically upregulated in AciCCs, and that active chromatin regions and gene expression signatures in AciCCs are highly correlated with the NR4A3 transcription factor binding motif. Overexpression of NR4A3 in mouse salivary gland cells increases expression of known NR4A3 target genes and has a stimulatory functional effect on cell proliferation. We conclude that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC.

Li ZY, Wang ZX, Li CC
Kinesin family member 20B regulates tongue cancer progression by promoting cell proliferation.
Mol Med Rep. 2019; 19(3):2202-2210 [PubMed] Free Access to Full Article Related Publications
Oral cancer refers to the malignant tumors that occur in the oral cavity, of which 80% are squamous cell carcinomas. The incidence of oral cancer accounts for ~5% of the incidence of systemic malignancies, with rapid progression, extensive infiltration and poor prognosis. In the present study, Kinesin family member (KIF)20B, a member of Kinesin‑6 family, was identified as a potential biomarker which could promote cancer progression. A total of 82 patients were recruited and KIF20B expression levels were investigated by immunohistochemistry, and were divided into high and low groups based on the median of KIF20B expression levels. The clinicopathological features and survival‑associated data of the two groups were analyzed and the results were provided as a table and by a Kaplan‑Meier plot, respectively. Additionally, KIF20B was successfully silenced in two tongue cancer cell lines, CAL‑27 and TCA‑8113. MTT and colony formation assay were performed to determine the changes of cell proliferation in knocked down‑KIF20B cell lines. In addition, proliferation‑associated proteins Ki67 and PCNA were investigated, by western blotting. In animal experiments, subcutaneous tumor formation was performed with control cells and cells with knocked down KIF20B, to determine the inhibitory effect of KIF20B in vivo. Firstly, it was found that there was significantly high expression levels of KIF20B in tongue cancer patients (P<0.05). Patients with high expression of KIF20B had poorer clinicopathological results including tumor differentiation level, lymph node metastasis and clinical stages. The overall survival and relapse‑free survival of high‑expression group were also poor. Secondly, after successful establishment of cells with knocked down KIF20B, this resulted in a notable reduction in cell proliferation in vitro. Subsequent western blotting further confirmed that Ki67 and PCNA expression levels had a significant decline. Finally, it was demonstrated that knocking down KIF20B could inhibit tumor volume growth in vivo. In conclusion, the high level of KIF20B in oral squamous cell carcinoma was significantly associated with poor clinicopathological features and survival. KIF20B might promote cancer development through enhancing cell proliferation in vitro, and might be a potential biomarker of oral squamous cell carcinoma.

Hsu CW, Chen YT, Hsieh YJ, et al.
Integrated analyses utilizing metabolomics and transcriptomics reveal perturbation of the polyamine pathway in oral cavity squamous cell carcinoma.
Anal Chim Acta. 2019; 1050:113-122 [PubMed] Related Publications
Oral cavity squamous cell carcinoma (OSCC), the most common malignancy of the oral cavity, is associated with poor prognosis and high mortality worldwide. Moreover, knowledge of the metabolic alterations that occur in OSCC is still limited. In the present study, we used a quantitative metabolomic approach with chemical isotope labeling (CIL) to analyze alterations in the metabolite levels in paired cancerous (T) and adjacent noncancerous (AN) tissues from 31 OSCC patients. Using volcano plot and orthogonal projections to latent structure-discriminant analysis (OPLS-DA), we uncovered 99 dysregulated metabolites in OSCC and verified the identities of seven metabolites via comparison with authenticated standards. From these seven metabolites, we constructed a 3-marker panel, consisting of putrescine, glycyl-leucine, and phenylalanine, using a support vector machine (SVM) model that can discriminate T from AN with high sensitivity and specificity based on receiver operator characteristic (ROC) analysis. Furthermore, by integrating the metabolomics profiles with transcriptomics data obtained from the same sample set, we revealed the dysregulation of the polyamine pathway in OSCC. Our findings provide insights into the metabolic perturbations present in OSCC and have uncovered potential metabolic biomarkers and therapeutic targets for use in the treatment of OSCC.

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