MicroRNA-455-5p Contributes to Cholangiocarcinoma Growth and Mediates Galangin's Anti-Tumor Effects

Xu Deng; Meiling Zuo; Zhifang Pei; Yuanlin Xie; Zhongbao Yang; Zhihui Zhang; Minna Jiang; Dabin Kuang

doi:10.7150/jca.58873

MicroRNA-455-5p Contributes to Cholangiocarcinoma Growth and Mediates Galangin's Anti-Tumor Effects

J Cancer. 2021 Jun 4;12(15):4710-4721. doi: 10.7150/jca.58873. eCollection 2021.

Authors

Xu Deng¹, Meiling Zuo², Zhifang Pei³, Yuanlin Xie², Zhongbao Yang², Zhihui Zhang¹, Minna Jiang³, Dabin Kuang²

Affiliations

¹ Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Pharmacy, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan, China.
³ Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Fully understanding the mechanism of how Cholangiocarcinoma (CCA) development and discovering promising therapeutic drugs are important to improve patients' survival time. This study identifies that microRNA-455-5p (miR-455-5p) targets protein phosphatase 1 regulatory subunit 12A (PPP1R12A), an effect that represses mitogen-activated protein kinase (MAPK) and PI3K/AKT pathway activation, thereby controlling CCA cells survival and metastasis. Moreover, miR-455-5p expression is reduced in CCA tissues and negative correlation with PPP1R12A and PPP1R12A knockdown phenotypic mimics miR-455-5p' effects on CCA cells. Furthermore, we demonstrate that galangin inhibits CCA growth both in vitro and in vivo, which is associated with increased miR-455-5p and repressed PPP1R12A expression. In support, overexpression of miR-455-5p abrogates those galangin-mediated anti-CCA effects. These findings establish an essential role of miR-455-5p in CCA development and galangin may provide a potential therapeutic adjuvant agent for anti-CCA treatment.

Keywords: cholangiocarcinoma; galangin; metastasis; microRNA; survival.