Silencing of microRNA-27a facilitates autophagy and apoptosis of melanoma cells through the activation of the SYK-dependent mTOR signaling pathway

沉默 microRNA-27a 通过激活 SYK 依赖性 mTOR 信号通路促进黑色素瘤细胞自噬和凋亡

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作者:Hua Tang, Xiaopeng Xu, Weirong Xiao, Yangying Liao, Xiao Xiao, Lan Li, Ke Li, Xiaomin Jia, Hao Feng

Abstract

Melanoma is considered as an aggressive neoplastic transformation and featured with high metastatic potential. Although some studies have provided targets for novel therapeutic interventions, clinical development of targeted drugs for melanoma still remains obscure. Therefore, this study aims to identify the role of microRNA-27a (miR-27a) in autophagy and apoptosis of melanoma cells in regulating spleen tyrosine kinase (SYK)-mediated the mammalian target of rapamycin (mTOR) signaling pathway. A microarray-based analysis was made to screen differentially expressed genes and predict target miRNA. Melanoma specimens were collected with pigmented nevus as a control. Melanoma cell line Mel-RM was treated with miR-27a inhibitor or pcDNA-SYK to prove their effects on autophagy and apoptosis of melanoma cells. The volume change and tumor mass of nude mice in each group were detected by the tumorigenesis assay. Microarray-based analysis results showed that SYK was lowly expressed in melanoma cells and may be regulated by miR-27a. Besides, miR-27a expression was increased whereas SYK expression was decreased in melanoma tissues. Meanwhile, miR-27a was positively correlated with tumor stage and lymph node metastasis of melanoma tissues. Furthermore, miR-27a targeted SYK and silencing of miR-27a or overexpression of SYK cells promoted autophagy and apoptosis of melanoma cells and reduced their tumorigenic ability in vivo. In conclusion, this study proves that silencing of miR-27a facilitates autophagy and apoptosis of melanoma cells by upregulating SYK expression and activating the mTOR signaling pathway. The finding offers new ideas for the clinical development of melanoma.

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