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Research Paper|Volume 11, Issue 11|pp 3639—3649

MORC2 promotes cell growth and metastasis in human cholangiocarcinoma and is negatively regulated by miR-186-5p

Guanqun Liao1,2,3, Xiaopeng Liu3, Dehai Wu4, Fangting Duan1, Xueyi Xie3, Shunqian Wen3, Yiqun Li3, Shengping Li1,2
  • 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
  • 2Department of Hepatobiliary and Pancreatic Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
  • 3Department of Hepatobiliary Surgery, Foshan Hospital Affiliated to Southern Medical University, Foshan 528000, P. R. China
  • 4Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin 528001, P. R. China
* Equal contribution
Received: February 17, 2019Accepted: May 27, 2019Published: June 9, 2019
https://doi.org/10.18632/aging.102003

Copyright: Liao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Microrchidia family CW-type zinc finger 2 (MORC2) is a ubiquitously expressed protein that contributes to chromatin remodeling, DNA repair, and lipogenesis. However, its role in cholangiocarcinoma (CCA) remains largely unknown. The aim of this study was to investigate the expression profile of MORC2 and its potential functions in CCA progression. The results showed that MORC2 was upregulated in human CCA specimens and cell lines. MORC2 expression was significantly associated with serum CA19-9 levels (P = 0.009), TNM stage (P = 0.003) and lymph node invasion (P = 0.004). Furthermore, high MORC2 expression was associated with poor 5-year survival (P = 0.016). Functional experiments revealed that MORC2 knockdown could suppress CCA cell proliferation, migration, and invasion both in vivo and in vitro. Mechanically, we found that MORC2 promoted CCA cell metastasis through the EMT process and enhanced proliferation via the Akt signaling pathway. Moreover, MORC2 was negatively regulated by miR-186-5p. MiR-186-5p could influence CCA cell proliferation, migration and metastasis by regulating MORC2. Taken together, the findings of this study demonstrated the oncogenic role of MORC2 in CCA tumorigenesis and metastasis, and clarified an underlying regulatory mechanism mediating MORC2 upregulation, which may provide a novel therapeutic target in CCA treatment.