Elevated microRNA-145 inhibits the development of oral squamous cell carcinoma through inactivating ERK/MAPK signaling pathway by down-regulating HOXA1.

Background: Oral cancer is one of the most frequent solid cancers worldwide, and oral squamous cell carcinoma (OSCC) constitutes approximately 90% of oral cancers. The discovery of reliable prognostic indicators would be a potential strategy for OSCC treatment. In the present study, we aim to explore the underlying mechanism by which microRNA-145 (miR-145) affected OSCC. Methods: Forty-eight patients diagnosed with OSCC were enrolled to obtain the OSCC tissues and adjacent normal tissues. The targeting relationship between miR-145 and Homeobox A1 (HOXA1) was verified. In order to assess the effects of miR-145 in OSCC and the detailed regulatory mechanism, the SCC-9 cell line was adopted, in which expression of miR-145 and HOXA1 were altered by transfection. Then, a series of in vitro and in vivo experiments were performed to evaluate the cell viability, migration, invasion, and tumor growth. Results: miR-145 was poorly expressed and HOXA1 was highly expressed in OSCC. HOXA1 was verified as a target of miR-145 to mediate the activation of the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) signaling pathway. In the circumstance of miR-145 elevation or HOXA1 depletion, the SCC-9 cell line manifested with inhibited cell viability, invasion, and migration in vitro, coupled with reduced tumor growth in vivo, with a decreased expression of ERK/MAPK signaling pathway-related genes/proteins. Conclusion: These findings suggested that miR-145 can inhibit HOXA1 to inactivate the ERK/MAPK signaling pathway, thereby suppressing OSCC cell proliferation, migration, and invasion to further inhibit the development of OSCC, highlighting a novel therapeutic target for the OSCC treatment.

Ding J ，Sun D ，Xie P 《-》

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 ... -  《-》

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》

Role of miR-218-GREM1 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma: An in vivo and vitro study based on microarray data.

Oral squamous cell carcinoma (OSCC) is a prevalent cancer that develops in the head and neck area and has high annual mortality despite optimal treatment. microRNA-218 (miR-218) is a tumour inhibiting non-coding RNA that has been reported to suppress the cell proliferation and invasion in various cancers. Thus, our study aims to determine the mechanism underlying the inhibitory role of miR-218 in OSCC. We conducted a bioinformatics analysis to screen differentially expressed genes in OSCC and their potential upstream miRNAs. After collection of surgical OSCC tissues, we detected GREM1 expression by immunohistochemistry, RT-qPCR and Western blot analysis, and miR-218 expression by RT-qPCR. The target relationship between miR-218 and GREM1 was assessed by dual-luciferase reporter gene assay. After loss- and gain-of-function experiments, OSCC cell proliferation, migration and invasion were determined by MTT assay, scratch test and Transwell assay, respectively. Expression of TGF-β1, Smad4, p21, E-cadherin, Vimentin and Snail was measured by RT-qPCR and Western blot analysis. Finally, effects of miR-218 and GREM1 on tumour formation and liver metastasis were evaluated in xenograft tumour-bearing nude mice. GREM1 was up-regulated, and miR-218 was down-regulated in OSCC tissues, and GREM1 was confirmed to be the target gene of miR-218. Furthermore, after up-regulating miR-218 or silencing GREM1, OSCC cell proliferation, migration and invasion were reduced. In addition, expression of TGF-β signalling pathway-related genes was diminished by overexpressing miR-218 or down-regulating GREM1. Finally, up-regulated miR-218 or down-regulated GREM1 reduced tumour growth and liver metastasis in vivo. Taken together, our findings suggest that the overexpression of miR-218 may inhibit OSCC progression by inactivating the GREM1-dependent TGF-β signalling pathway.

Wang Y ，Jiang Y ，Chen L 《-》

MiR-376c-3p regulates the proliferation, invasion, migration, cell cycle and apoptosis of human oral squamous cancer cells by suppressing HOXB7.

To test the influence of miR-376c-3p on the proliferation, invasion, migration, cell cycle and apoptosis of human oral squamous cancer cells (OSCC) and the relevant mechanism. We applied qRT-PCR and Western blot to compare the expression level of miR-376c-3p and HOXB7 in SCC-4, SCC-9, SCC-15, SCC-25 OSCC cell lines and 49 paired OSCC and normal oral epithelial tissue specimens were included in our present study. Also we analyzed the relative relationship of expression level between miR-376c-3p and HOXB7 in cancer tissues. Luciferase assay was used to confirm the target relationship between miR-376c-3p and HOXB7. Besides, MTT, Transwell, wound healing, colony formation and flow cytometer experiments were applied to evaluate the proliferation, cell viability, apoptosis, invasion and migration of transfected OSCC. MiR-376c-3p was down-regulated while HOXB7 was up-regulated in OSCC tissues and cells than the normal ones. MiR-376c-3p directly targeted HOXB7 and reduced the expression of HOXB7. Overexpression of miR-376c-3p attenuated proliferation of SCC-9, SCC-15, SCC-24 and SCC-25 cells. Moreover, miR-376c-3p suppressed proliferation, viability, migration and invasion and induced G1/G0 arrest and cell apoptosis of SCC-25 cells. Besides, overexpression of HOXB7 efficiently abrogates these influences caused by overexpression of miR-376c-3p. MiR-376c-3p suppresses the fission, proliferation, migration and invasion and induces cell apoptosis of OSCC via targeting HOXB7.

Wang K ，Jin J ，Ma T ，Zhai H ... -  《-》