MicroRNA-375 Inhibits Growth and Enhances Radiosensitivity in Oral Squamous Cell Carcinoma by Targeting Insulin Like Growth Factor 1 Receptor.

MicroRNAs (miRNAs) have emerged as key players in various human biological processes, including tumorigenesis. Here, we investigated the roles of miR-375 in the pathogenesis of oral squamous cell carcinoma (OSCC). We performed quantitative real-time PCR (qRT-PCR) to detect miR-375 expression in OSCC tissues and corresponding normal oral epithelial tissues and analyze the correlation of miR-375 expression with OSCC metastasis and patient's survival. Then, the effects of miR-375 expression on proliferation, cell cycle, apoptosis and radiosensitivity in OSCC cells were determined by using MTT, flow cytometry and clonogenic survival assays. A dual-luciferase reporter assay was performed to test whether miR-375 binds to the 3'-untranslated region (3'-UTR) of target mRNA. The expression level of miR-375 in OSCC tissues was significantly lower than that in normal oral epithelial tissues, and low miR-375 expression was correlated with higher incidence of lymph node metastasis and poor survival of OSCC patients. Upregulation of miR-375 significantly inhibits growth, induces cell cycle arrest in G0/G1 phase, increases apoptosis and enhances radiosensitivity in OSCC cells. Analysis of luciferase activity demonstrated that miR-375 binds to the 3'-UTR of insulin like growth factor 1 receptor (IGF-1R). Small interfering RNA (shRNA)-mediated IGF-1R knockdown mimics the effects of miR-375 upregulation, while overexpression of IGF-1R partially reverses those effects in OSCC cells. It was obviously demonstrated that miRNA-375 inhibits growth and enhances radiosensitivity in OSCC cells by targeting IGF-1R, suggesting that miR-375 may be a potential therapeutic target for OSCC patients.

Zhang B ，Li Y ，Hou D ，Shi Q ，Yang S ，Li Q ... -  《-》

MiR-148a inhibits oral squamous cell carcinoma progression through ERK/MAPK pathway via targeting IGF-IR.

The current study aimed to investigate the functional roles and clinical significance of microRNA-148a (miR-148a) in the progression of oral squamous cell carcinoma (OSCC). Relative expression of miR-148a in OSCC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was performed to estimate the relationship between miR-148a expression and clinical characteristics of OSCC patients. Cell transfection was carried out using Lipofectamine® 2000. Biological behaviors of tumor cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays. Bioinformatics analysis and luciferase reporter assay were used to identify the target genes of miR-148a. Protein expression was detected through Western blot analysis. MiR-148a expression was obviously decreased in OSCC tissues and cells, and such down-regulation was closely correlated with lymph node metastasis (P=0.027) and tumor node metastasis (TNM) stage (P=0.001) of OSCC patients. miR-148a overexpression could significantly impair OSCC cell proliferation, migration and invasion in vitro (P<0.05 for all). Insulin-like growth factor-I receptor (IGF-IR) was a potential target of miR-148a. MiR-148a could inhibit ERK/MAPK signaling pathway through targeting IGF-IR. MiR-148a plays an anti-tumor role in OSCC and inhibits OSCC progression through suppressing ERK/MAPK pathway via targeting IGF-IR.

Jia T ，Ren Y ，Wang F ，Zhao R ，Qiao B ，Xing L ，Ou L ，Guo B ... -  《-》

miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells.

Weng JH ，Yu CC ，Lee YC ，Lin CW ，Chang WW ，Kuo YL ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Reciprocal regulation of microRNA-99a and insulin-like growth factor I receptor signaling in oral squamous cell carcinoma cells.

Yen YC ，Shiah SG ，Chu HC ，Hsu YM ，Hsiao JR ，Chang JY ，Hung WC ，Liao CT ，Cheng AJ ，Lu YC ，Chen YW ... -  《Molecular Cancer》

MiR-92a regulates oral squamous cell carcinoma (OSCC) cell growth by targeting FOXP1 expression.

Increasing evidence indicates that microRNAs dysregulation contributes to the development and progression of various human cancers, including oral squamous cell carcinoma (OSCC). However, little is known about the potential role of microRNA-92a (miR-92a) in OSCC. Thus, the aim of this study was to investigate the effects of miR-92a expression on OSCC cell growth, apoptosis and tumorigenesis. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-92a in primary tumor tissues and OSCC cell lines. The effects of miR-92a on cell proliferation, cell cycle, apoptosis and tumorigenesis of OSCC cells were explored after miR-92a expression was increased or decreased in the UM1 and Tca-8113 cells, respectively. The 3'-untranslated region (3'-UTR) of FOXP1 combined with miR-92a was analyzed with dual-luciferase reporter assays. The level of miR-92a expression was significantly up-regulated in the OSCC tissues and cell lines. The up-regulation of miR-92a expression promoted UM1 cell proliferation, cell cycle progression in vitro and tumor growth in nude mice, but its expression reduction inhibited these processes and induced apoptosis in Tca-8113 cells. Additionally, miR-92a expression was inversely correlated with FOXP1 protein expression in the OSCC tissues and cell lines. Furthermore, FOXP1 was identified as a functional downstream target of miR-92a by directly targeting the 3'-UTR of FOXP1. These findings indicate that miR-92a may act as a tumor inducer in OSCC by suppressing FOXP1 expression, and it could serve as a potential therapeutic target for OSCC treatment.

Guo J ，Wen N ，Yang S ，Guan X ，Cang S ... -  《-》