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

Overview

Journal Theranostics

Date 2017 Jul 26

PMID 28740547

Citations 45

Authors

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

Affiliations

Soon will be listed here.

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 . 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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References

Dickson P, Gershenwald J . Staging and prognosis of cutaneous melanoma. Surg Oncol Clin N Am. 2010; 20(1):1-17. PMC: 3221385. DOI: 10.1016/j.soc.2010.09.007. View

Li J, Aung L, Long B, Qin D, An S, Li P . miR-23a binds to p53 and enhances its association with miR-128 promoter. Sci Rep. 2015; 5:16422. PMC: 4639766. DOI: 10.1038/srep16422. View

Kim H, Kim M, Kim E, Yang Y, Lee M, Lim J . Berberine-induced AMPK activation inhibits the metastatic potential of melanoma cells via reduction of ERK activity and COX-2 protein expression. Biochem Pharmacol. 2011; 83(3):385-94. DOI: 10.1016/j.bcp.2011.11.008. View

Otomo C, Metlagel Z, Takaesu G, Otomo T . Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat Struct Mol Biol. 2012; 20(1):59-66. PMC: 3540207. DOI: 10.1038/nsmb.2431. View

Orgaz J, Sanz-Moreno V . Emerging molecular targets in melanoma invasion and metastasis. Pigment Cell Melanoma Res. 2012; 26(1):39-57. DOI: 10.1111/pcmr.12041. View

Lock R, Kenific C, Leidal A, Salas E, Debnath J . Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov. 2014; 4(4):466-79. PMC: 3980002. DOI: 10.1158/2159-8290.CD-13-0841. View

Wang B, Hsu S, Frankel W, Ghoshal K, Jacob S . Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. Hepatology. 2012; 56(1):186-97. PMC: 3355233. DOI: 10.1002/hep.25632. View

Liu N, Sun Q, Chen J, Li J, Zeng Y, Zhai S . MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway. Oncol Rep. 2012; 28(3):961-8. DOI: 10.3892/or.2012.1905. View

Gimotty P, van Belle P, Elder D, Murry T, Montone K, Xu X . Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma. J Clin Oncol. 2005; 23(31):8048-56. DOI: 10.1200/JCO.2005.02.0735. View

10.

Dynoodt P, Speeckaert R, de Wever O, Chevolet I, Brochez L, Lambert J . miR-145 overexpression suppresses the migration and invasion of metastatic melanoma cells. Int J Oncol. 2013; 42(4):1443-51. DOI: 10.3892/ijo.2013.1823. View

11.

Qiang L, Zhao B, Ming M, Wang N, He T, Hwang S . Regulation of cell proliferation and migration by p62 through stabilization of Twist1. Proc Natl Acad Sci U S A. 2014; 111(25):9241-6. PMC: 4078859. DOI: 10.1073/pnas.1322913111. View

12.

Lv Q, Hua F, Hu Z . DEDD, a novel tumor repressor, reverses epithelial-mesenchymal transition by activating selective autophagy. Autophagy. 2012; 8(11):1675-6. PMC: 3494596. DOI: 10.4161/auto.21438. View

13.

Hassan M, Gordon J, Beloti M, Croce C, van Wijnen A, Stein J . A network connecting Runx2, SATB2, and the miR-23a~27a~24-2 cluster regulates the osteoblast differentiation program. Proc Natl Acad Sci U S A. 2010; 107(46):19879-84. PMC: 2993380. DOI: 10.1073/pnas.1007698107. View

14.

Wang H, Guan X, Tu Y, Zheng S, Long J, Li S . MicroRNA-29b attenuates non-small cell lung cancer metastasis by targeting matrix metalloproteinase 2 and PTEN. J Exp Clin Cancer Res. 2015; 34:59. PMC: 4469413. DOI: 10.1186/s13046-015-0169-y. View

15.

Kanemaru H, Fukushima S, Yamashita J, Honda N, Oyama R, Kakimoto A . The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci. 2011; 61(3):187-93. DOI: 10.1016/j.jdermsci.2010.12.010. View

16.

Ostmeier H, Fuchs B, Otto F, Mawick R, Lippold A, Krieg V . Prognostic immunohistochemical markers of primary human melanomas. Br J Dermatol. 2001; 145(2):203-9. DOI: 10.1046/j.1365-2133.2001.04335.x. View

17.

Hatzl S, Geiger O, Kuepper M, Caraffini V, Seime T, Furlan T . Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP. Cancer Res. 2016; 76(12):3644-54. PMC: 5024755. DOI: 10.1158/0008-5472.CAN-15-3049. View

18.

Schaffer B, Levin R, Hertz N, Maures T, Schoof M, Hollstein P . Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction. Cell Metab. 2015; 22(5):907-21. PMC: 4635044. DOI: 10.1016/j.cmet.2015.09.009. View

19.

Messina J, Yu H, Riker A, Munster P, Jove R, Daud A . Activated stat-3 in melanoma. Cancer Control. 2008; 15(3):196-201. DOI: 10.1177/107327480801500302. View

20.

Le Gal K, Ibrahim M, Wiel C, Sayin V, Akula M, Karlsson C . Antioxidants can increase melanoma metastasis in mice. Sci Transl Med. 2015; 7(308):308re8. DOI: 10.1126/scitranslmed.aad3740. View