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

Ma, Meng; Dai, Jie; Tang, Huan; Xu, Tianxiao; Yu, Sifan; Si, Lu; Cui, Chuanliang; Sheng, Xinan; Chi, Zhihong; Mao, Lili; Wu, Xiaowen; Yang, Lu; Yu, Huan; Li, Siming; Lian, Bin; Tang, Bixiang; Wang, Xuan; Yan, Xieqiao; Bai, Xue; Zhou, Li; Kong, Yan; Guo, Jun

doi:10.7150/thno.30516

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

Research Paper

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

Meng Ma^1,2*, Jie Dai^1*, 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 Kong^1✉, Jun Guo^1✉

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

Citation:

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. https://www.thno.org/v09p0945.htm

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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

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APA

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. (2019). MicroRNA-23a-3p Inhibits Mucosal Melanoma Growth and Progression through Targeting Adenylate Cyclase 1 and Attenuating cAMP and MAPK Pathways. Theranostics, 9(4), 945-960. https://doi.org/10.7150/thno.30516.

ACS

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.

NLM

CSE

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. 2019. MicroRNA-23a-3p Inhibits Mucosal Melanoma Growth and Progression through Targeting Adenylate Cyclase 1 and Attenuating cAMP and MAPK Pathways. Theranostics. 9(4):945-960.

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