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.

中文翻译：

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下调的miR-23a通过促进自噬促进皮肤黑色素瘤的转移。

黑色素瘤是最具侵袭性的肿瘤之一，转移的发生导致患者生存率急剧下降。因此，与转移相关的生物标志物和治疗靶标的鉴定将对改善黑色素瘤治疗学做出很大贡献。最近，微小RNA（miRNA）已参与调节癌症的侵袭和转移，并被证明是血清中各种肿瘤的潜在非侵入性生物标志物。在这里，我们报道了miR-23a作为一种新型的转移相关miRNA，在调节黑素瘤的侵袭和转移能力中发挥了重要作用，在预测黑素瘤的转移和预后方面具有重要价值。我们发现转移性黑色素瘤患者的血清miR-23a水平显着下调，并且与不良的临床结果高度相关。此外，在转移性黑素瘤组织和细胞系中，miR-23a水平也显着降低。此外，过表达的miR-23a通过直接靶向ATG12来消除自噬，从而抑制了黑素瘤细胞的侵袭和迁移特性。特别地，miR-23a-ATG12轴通过自噬介导的AMPK-RhoA途径减弱了黑色素瘤的侵袭和迁移。最后，miR-23a的过表达可预防黑色素瘤转移体内。综上所述，我们的研究结果表明，与转移相关的miR-23a不仅是潜在的生物标志物，而且还是黑色素瘤的重要治疗靶标。