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

Theranostics. 2017 Jun 1;7(8):2231-2249. doi: 10.7150/thno.18835. eCollection 2017.


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.

Keywords: autophagy; biomarker; melanoma; metastasis.; miR-23a.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Autophagy*
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Melanoma / secondary*
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / blood
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Metastasis / physiopathology*
  • Skin Neoplasms / secondary*
  • Tumor Cells, Cultured


  • MIRN23a microRNA, human
  • MicroRNAs