miR-194 is a negative regulator of GEF-H1 pathway in melanoma

Abstract

The incidence and associated mortality of melanoma continues to increase worldwide. At present, there is no curative therapy for advanced stage of melanoma. It is necessary to find new indicators of prognosis and therapeutic targets. Increasing evidence shows that miRNA can provide potential candidate biomarkers for melanoma and therapeutic targets. GEF-H1, a regulator of RhoA, as oncogenic driver in melanoma, promotes the growth and invasion of melanoma. miR-194 is a tumor-suppressor gene in multiple tumors, such as bladder and non-small cell lung cancer, and clear cell renal cell carcinoma. In the present study, we demonstrated that GEF-H1 serves as target of miR-194. Overexpression of miR-194 downregulates the GEF-H1/RhoA pathway, inhibits melanoma cancer cell proliferation and metastasis. Furthermore, miR-194 expression is negatively associated with tumor-node-metastasis (TNM) stages. Briefly, our findings provided new theoretical basis for melanoma treatment.

MicroRNAs as Potential Biomarkers for Chemoresistance in Adenocarcinomas of the Esophagogastric Junction

“…In addition, we correlated the miRNA expression with patients' overall survival and could demonstrate that overall survival was significantly correlated with expression levels of hsa-miRNA-194-5p (p value <0.0001) although independence could not be demonstrated applying Cox regression analysis (p � 0.462; hazard ratio 1.469; 95% confidence interval 0.527-4.096). In accordance with our results, where higher levels of hsa-miRNA-194-5p corresponded to prolonged survival (97.67 months vs. 32.69 months), overexpression has been reported to inhibit cell proliferation and to act as a tumor suppressor in laryngeal SCC, prostate cancer, melanoma, bladder cancer, NSCLC, and clear cell renal carcinoma [83][84][85][86][87]. In addition, overexpression has been found to inhibit growth and proliferation in gastric cancer cell lines and esophageal squamous cell carcinoma [88,89].…”

Application values of miR-194 and miR-29 in the diagnosis and prognosis of gastric cancer

“…Studies have shown that miR-194 is downregulated in non-small cell lung cancer and clear cell renal cell carcinoma (ccRCC), and the reduced expression level is closely related to prognosis ( 18 , 19 ). Low expression levels of miR-194 was detected in ovarian cancer, colorectal cancer, melanoma and other tumors, and miR-194 can participate in the regulation of drug sensitivity and tumor growth through a series of signal pathways ( 20 – 22 ).…”

MicroRNA-194 modulates epithelial&ndash;mesenchymal transition in human colorectal cancer metastasis

“…The involvement of miR-194 has been demonstrated in the origination and progression in certain varieties of cancer 22,23. To investigate the functional roles of miR-194 in CRC cell lines, we constructed miR-194 stably expressing SW480 cells.…”