Theranostics 2019; 9(4):945-960. doi:10.7150/thno.30516

Research Paper

MicroRNA-23a-3p Inhibits Mucosal Melanoma Growth and Progression through Targeting Adenylate Cyclase 1 and Attenuating cAMP and MAPK Pathways

Meng Ma1,2*, Jie Dai1*, Huan Tang1, Tianxiao Xu1, Sifan Yu1, Lu Si1, Chuanliang Cui1, Xinan Sheng1, Zhihong Chi1, Lili Mao1, Xiaowen Wu1, Lu Yang1, Huan Yu1, Siming Li1, Bin Lian1, Bixiang Tang1, Xuan Wang1, Xieqiao Yan1, Xue Bai1, Li Zhou1, Yan Kong1✉, Jun Guo1✉

1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing 100142, China
2. Department of Radiotherapy, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
*M. Ma and J. Dai contributed equally to this work

Abstract

Mucosal melanoma (MM) is the second most common melanoma subtype in Asian populations. Deregulation of microRNAs (miRNAs) has been extensively investigated in various cancers, including cutaneous melanoma. However, the roles of miRNAs in MM are unclear. In this study, we carried out miRNA profiling in MM, and we investigated the clinical and biological roles of miR-23a-3p in MM.

Methods: miRNA expression in MM was profiled by miRNA microarray analysis. The expression of miR-23a-3p was quantitated by qRT-PCR in a cohort of 117 patients with MM, and its prognostic significance was evaluated. The biological effect of miR-23a-3p was demonstrated by both in vitro and in vivo studies through ectopic expression of miR-23a-3p. The target gene of miR-23a-3p and molecular pathway influenced by it was characterized using in silico target prediction tools, dual luciferase reporter assays, knockdown, and rescue experiments.

Results: Microarray and qRT-PCR results showed that the miR-23a-3p level was substantially lower in MM, and low miR-23a-3p expression was significantly associated with poor outcomes. Ectopic expression of miR-23a-3p suppressed MM cell proliferation, migration, invasion, and tumorigenicity, indicating that miR-23a-3p has a tumor-suppressive role in MM. Mechanistic investigations identified adenylate cyclase 1 (ADCY1) as a direct target of miR-23a-3p in MM, and knockdown of ADCY1 recapitulated all the phenotypic characteristics of miR-23a-3p overexpression. Targeting of ADCY1 by miR-23a-3p resulted in the suppression of cyclic adenosine monophosphate (cAMP) and mitogen-activated protein kinase (MAPK) signaling pathways.

Conclusions: Our data highlight the molecular etiology and clinical significance of miR-23a-3p in MM and reveal its major target and biological function. miR-23a-3p may represent a new prognostic biomarker or therapeutic target in MM.

Keywords: miR-23a-3p, ADCY1, mucosal melanoma, cAMP, MAPK

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Ma M, Dai J, Tang H, Xu T, Yu S, Si L, Cui C, Sheng X, Chi Z, Mao L, Wu X, Yang L, Yu H, Li S, Lian B, Tang B, Wang X, Yan X, Bai X, Zhou L, Kong Y, Guo J. MicroRNA-23a-3p Inhibits Mucosal Melanoma Growth and Progression through Targeting Adenylate Cyclase 1 and Attenuating cAMP and MAPK Pathways. Theranostics 2019; 9(4):945-960. doi:10.7150/thno.30516. Available from http://www.thno.org/v09p0945.htm