Amplification and up-regulation of microRNA-30b in oral squamous cell cancers.

MicroRNAs (miRNAs) are negative regulators of protein coding genes which are frequently deregulated in mammary cancers. Over-expression of microRNA-30b (hsa-miR-30b) is implicated in tumour invasion and immunosuppression during metastasis. The chromosome locus of MIR30B gene, 8q24, is frequently amplified in oral squamous cell cancers (OSCCs). In the present study, we aimed to investigate the copy number variations as well as expression levels of MIR30B gene in OSCCs and analyse their correlation with tumour stage. Quantitative real-time PCR was performed to examine the copy number of MIR-30B gene as well as hsa-miR-30b expression in 107 OSCC samples with matched adjacent normal tissues. Proportional odds regression and two-way repeated measurement ANOVA were used to analyse the association between copy number variations (CNVs) and hsa-miR-30b expression. Copy number gains of MIR-30B gene were detected in a relatively large percentage of the OSCC samples (27.1%, 29 out of 107) and were correlated with tumour stages (p<0.001). MIR30B gene amplification also showed a close correlation with hsa-miR-30b over-expression in OSCCs (p<0.001). On the other hand, enhanced miR-30b expression was also detected in a group of OSCC samples with unaltered copy number of MIR30B gene. Copy number increase of MIR30B is frequent in advanced OSCC and is correlated with hsa-miR-30b over-expression. Sporadic OSCCs can exhibit different mechanisms of MIR30B regulation.

Shao C ，Yu Y ，Yu L ，Pei Y ，Feng Q ，Chu F ，Fang Z ，Zhou Y ... -  《-》

ERBB2 gene amplification in oral squamous cell malignancies: a correlation with tumor progression and gene expression.

Chromosomal instability is hallmark of carcinoma. Amplification of chromosome 17q11-q12 is present in some oral squamous cell cancer (OSCC) cases. In this study, we investigated the copy number variations of ERBB2 gene, which is located at this locus in collected OSCC samples and their correlation with tumor progression and gene expression. Quantitative real-time polymerase chain reaction was performed to detect the copy number of ERBB2 gene and the mRNA expression in 92 OSCC samples with matched adjacent normal tissues (ANTs). Proportional odds regression and 2-way repeated measurement analysis of variance were used to analyze the association between copy number variations and mRNA expression of the targeted gene. Copy number gains of ERBB2 were detected in some of the OSCCs (19.6%, 18/92) and correlated with tumor stage (P < .001). Copy number gains of ERBB2 also showed a positive correlation with mRNA overexpression in OSCCs (P < .001). However, enhanced ERBB2 mRNA expression was also detected in a group of OSCC samples with unaltered copy number of ERBB2 gene (P < .05). Copy number increase of ERBB2 is observed in OSCCs and correlates with gene overexpression in these tumors. In addition, overexpression of ERBB2 is also observed in some OSCCs that lack copy number changes, indicating involvement of another mechanism.

Chu F ，Feng Q ，Qian Y ，Zhang C ，Fang Z ，Shen G ... -  《-》

Connective tissue growth factor modulates oral squamous cell carcinoma invasion by activating a miR-504/FOXP1 signalling.

Yang MH ，Lin BR ，Chang CH ，Chen ST ，Lin SK ，Kuo MY ，Jeng YM ，Kuo ML ，Chang CC ... -  《-》

Up-regulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance.

Survivin, a key member of the inhibitor of apoptosis protein family, has been reported to be capable of regulating both cellular proliferation and apoptotic cell death. This protein is found to be overexpressed in many human cancers. The aim of this study was to evaluate the prognostic significance of survivin mRNA expression in oral squamous cell carcinoma (OSCC) and to analyze its correlation with chemoresistance. Reverse-transcription polymerase chain reaction assay was performed to detect the expression of survivin mRNA in OSCC cell lines or tissue samples. Immunohistochemistry was performed to detect the expression of survivin protein in OSCC tissues or corresponding nontumor tissues. Then the correlation between survivin mRNA expression and clinicopathologic features or prognosis of OSCC patients was analyzed. Small interfering RNA technology was used to down-regulate the expression of the survivin gene in the OSCC cell line. Methylthiazol tetrazolium and flow cytometric assays were performed to detect proliferation and apoptosis of the OSCC cell line (HSC-3). Furthermore, the effect of small interfering RNA (siRNA) targeting survivin on the sensitivity of OSCC cells to chemotherapeutic agents (cisplatin and 5-fluorouracil [5-FU]) was determined. Results showed that the levels of survivin mRNA expression were significantly higher in OSCC cells or tissues than those in normal human oral keratinocyte or corresponding noncancerous tissues. The immunostaining of survivin protein was significantly stronger in OSCC tissues than in corresponding nontumor tissues. Moreover, high survivin mRNA expression was correlated with poorer tumor differentiation, higher clinical stage, and the presence of lymph node metastasis (P < .05). Multivariate analysis showed that the status of survivin mRNA could be an independent prognostic factor for OSCC patients (hazard ratio 2.71, 95% confidence interval 1.46-5.10; P = .012). In addition, siRNA-mediated survivin down-regulation could significantly inhibit proliferation and induce apoptosis of OSCC cells. Suvivin down-regulation could also significantly enhance chemosensitivity of OSCC cells, which was associated with apoptosis enhancement. Thus, the status of survivin mRNA expression was a potential prognostic factor for OSCC patients, and siRNA-mediated survivin down-regulation could become a novel strategy for chemosensitization of human OSCCs.

Su L ，Wang Y ，Xiao M ，Lin Y ，Yu L ... -  《-》

miRNA expression profiles of oral squamous cell carcinomas.

Gombos K ，Horváth R ，Szele E ，Juhász K ，Gocze K ，Somlai K ，Pajkos G ，Ember I ，Olasz L ... -  《-》