Down-regulated miR-23a Contributes to the Metastasis of Cutaneous Melanoma by Promoting Autophagy.
Down-regulated miR-23a Contributes to the Metastasis of Cutaneous Melanoma by Promoting Autophagy.
复制标题
下调的 miR-23a 通过促进自噬促进皮肤黑色素瘤的转移
作者：
Guo W;Wang H;Yang Y;Guo S;Zhang W;Liu Y;Yi X;Ma J;Zhao T;Liu L;Jian Z;Liu L;Wang G;Gao T;Shi Q;Li C
黑色素瘤是最具侵袭性的肿瘤之一，转移的发生会导致患者的生存期急剧下降。因此，确定转移相关的生物标志物和治疗靶点将有助于提高黑色素瘤的治疗效果。近年来，microRNAs （miRNAs）已被证实与肿瘤侵袭和转移有关，是多种肿瘤血清中潜在的非侵入性生物标志物。在这里，我们报道了miR-23a作为一种新的与转移相关的miRNA，在调节黑色素瘤的侵袭和转移能力方面发挥着显著作用，在预测黑色素瘤的转移和预后方面具有重要价值。我们发现血清miR-23a水平在转移性黑色素瘤患者中显著下调，并与临床预后不良高度相关。此外，miR-23a水平在转移性黑色素瘤组织和细胞系中也显著降低。此外，过表达的miR-23a通过直接靶向ATG12来消除自噬，从而抑制黑色素瘤细胞的侵袭性和迁移性。特别是，miR-23a-ATG12轴通过自噬介导的AMPK-RhoA途径减弱黑色素瘤的侵袭和迁移。最后，miR-23a的过表达在体内阻止了黑色素瘤的转移。综上所述，我们的研究结果表明，转移相关的miR-23a不仅是一个潜在的生物标志物，也是一个有价值的黑色素瘤治疗靶点。
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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影响因子：
10.5
作者：
Guo, Jessie Yanxiang;Chen, Hsin-Yi;White, Eileen
通讯作者：
White, Eileen
影响因子：
2
作者：
Caltabiano, Rosario;Puzzo, Lidia;Longo, Antonio
通讯作者：
Longo, Antonio
血清 miR-16：预测黑色素瘤预后的潜在生物标志物
影响因子：
6.5
作者：
Guo, Sen;Guo, Weinan;Li, Chunying
通讯作者：
Li, Chunying
影响因子：
9.7
作者：
Boregowda, Rajeev K.;Olabisi, Oyenike O.;Abushahba, Walid;Jeong, Byeong-Seon;Haenssen, Keneshia K.;Chen, Wenjin;Chekmareva, Marina;Lasfar, Ahmed;Foran, David J.;Goydos, James S.;Cohen-Solal, Karine A.
通讯作者：
Cohen-Solal, Karine A.
影响因子：
6.2
作者：
Hazan, C;Melzer, K;Polsky, D
通讯作者：
Polsky, D