Down-regulated miR-23a Contributes to the Metastasis of Cutaneous Melanoma by Promoting Autophagy

下调 miR-23a 通过促进自噬促进皮肤黑色素瘤的转移

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作者:Weinan Guo, Huina Wang, Yuqi Yang, Sen Guo, Weigang Zhang, Yu Liu, Xiuli Yi, Jingjing Ma, Tao Zhao, Lin Liu, Zhe Jian, Ling Liu, Gang Wang, Tianwen Gao, Qiong Shi, Chunying Li

Abstract

Melanoma is among the most aggressive tumors, and the occurrence of metastasis leads to a precipitous drop in the patients' survival. Therefore, identification of metastasis-associated biomarkers and therapeutic targets will contribute a lot to improving melanoma theranostics. Recently, microRNAs (miRNAs) have been implicated in modulating cancer invasion and metastasis, and are proved as potential non-invasive biomarkers in sera for various tumors. Here, we reported miR-23a as a novel metastasis-associated miRNA that played a remarkable role in modulating melanoma invasive and metastatic capacity and was of great value in predicting melanoma metastasis and prognosis. We found that serum miR-23a level was significantly down-regulated in metastatic melanoma patients and highly correlated with poor clinical outcomes. In addition, miR-23a level was also remarkably decreased in metastatic melanoma tissues and cell lines. Furthermore, overexpressed miR-23a suppressed the invasive and migratory property of melanoma cells by abrogating autophagy through directly targeting ATG12. Specially, miR-23a-ATG12 axis attenuated melanoma invasion and migration through autophagy-mediated AMPK-RhoA pathway. Finally, the overexpression of miR-23a prevented melanoma metastasis in vivo. Taken together, our findings demonstrate that the metastasis-associated miR-23a is not only a potential biomarker, but also a valuable therapeutic target for melanoma.

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