miR-21 inhibitor sensitizes human OSCC cells to cisplatin.
ABSTRACT miR-21 as a tumor oncogenic molecule has been reported. However, whether miR-21 can affect the sensitivity of oral squamous cell carcinoma (OSCC) cells to cisplatin remain unclear. The aim of this study is to evaluate the roles of miR-21 in the sensitivity of OSCC cells to cisplatin. RT-PCR assay was performed to detect the expression of miR-21 in 10 pairs of OSCC and noncancerous tissue samples. Then As-miR-21 oligonucleotides were used to down the miR-21 expression. Finally, the effects of miR-21 downregulation the sensitivity of OSCC cells (CA-27) to cisplatin in vitro were also detected. The level of miR-21 expression in OSCC tissues was significantly higher than that in corresponding noncancerous tissues. Down the expression of miR-21 could significantly inhibit growth and induce apoptosis of CA-27 cells. Moreover, downregulation of miR-21 could sensitize CA-27 cells to cisplatin possibly by increasing cisplatin induced apoptosis. This study demonstrated that combination of cisplatin application with miR-21 downregulation might be a potential strategy for the treatment of human OSCC.
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ABSTRACT: OBJECTIVES: To identify differentially expressed miRNA between oral squamous cell carcinoma (OSCC) and non-cancer (NC) and to associate these with clinico-pathological parameters. MATERIALS AND METHODS: miRNA microarray profiling was utilized to obtain the expression profile of miRNAs in four OSCC and four NC samples. The expression of miR-31 and miR-375 was further validated in 26 OSCC and three NC samples using real-time-PCR. The association between miRNA expression and clinico-pathological parameters was tested by univariate and multivariate analyses. RESULTS: Microarray profiling demonstrated that 15 and four miRNAs were up-regulated and down-regulated, respectively, in OSCC as compared with NC. miR-31 and miR-375 were validated as up- and down-regulated miRNAs, respectively. In univariate analyses, expression of miR-31 was significantly elevated in early stage, tumours with no metastatic nodes and those from the buccal mucosa. By contrast, low miR-375 expression was significantly associated with late stage disease, larger tumour size and the non-cohesive type of pattern of invasion in OSCC. The association between miR-31 expression with tumour staging and site and miR-375 with tumour staging remained significant in multivariate analyses. CONCLUSIONS: This study has identified 19 miRNAs significantly associated with OSCC, and expressions of miR-31 and miR-375 were significantly related with clinico-pathological parameters suggesting they could be important in driving oral tumourigenesis.Oral Diseases 04/2013; · 2.38 Impact Factor
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ABSTRACT: Chemoresistance is a challenge for clinician in management of tongue cancer. Therefore, it is necessary to explore alternative therapeutic methods to overcome drug resistance. miRNAs are endogenous -22nt RNAs that play important regulatory roles by targeting mRNAs. miR-21, an essential oncogenic molecule, is associated with chemosensitivity of several human cancer cells to anticancer agents. In this study, we investigated the effects and molecular mechanisms of miR-21 in chemosensitivity of tongue squamous cell carcinoma cells (TSCC) to cisplatin. miR-21 expression was detected in tongue cancer tissue using RT-PCR and PDCD4 protein expression was measured using immunohistochemistry. miR-21 and(or) PDCD4 depleted cell lines were generated using miR-21 inhibitor and(or) siRNA. The viabilities of treated cells were analyzed using MTT assay. RT-PCR was used to detect miR-21 expression and immunoblotting was used to detect protein levels. Cell cycle and apoptosis were analyzed using propidium iodide (PI) staining and Annexin V/PI staining, respectively. The expression of miR-21 in tumorous tissue was significantly higher compared with adjacent normal tissue and loss of PDCD4 expression was observed in TSCCs. Transfection of miR-21 inhibitor induced sensitivity of TSCC cells (Tca8113 and CAL-27) to cisplatin. TSCC cells transfected with PDCD4 siRNA became more resistant to cisplatin therapy. We found an increase PDCD4 protein level following the transfection of miR-21 inhibitor using Western blot analysis. In addition, the enhanced growth-inhibitory effect by miR-21 inhibitor was weakened after the addition of PDCD4 siRNA. Suppression of miR-21 or PDCD4 could significantly promote or reduce cisplatin-induced apoptosis, respectively. Our data suggest that miR-21 could modulate chemosensitivity of TSCC cells to cisplatin by targeting PDCD4, and miR-21 may serve as a potential target for TSCC therapy.Molecular and Cellular Biochemistry 03/2014; · 2.33 Impact Factor