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微小RNA-455-5p促进胆管癌生长并介导高良姜素的抗肿瘤作用。

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

作者信息

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

机构信息

Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Department of Pharmacy, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan, China.

出版信息

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

DOI:10.7150/jca.58873
PMID:34149934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8210562/
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 and , 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.

摘要

全面了解胆管癌（CCA）的发展机制并发现有前景的治疗药物对于延长患者生存时间至关重要。本研究发现，微小RNA-455-5p（miR-455-5p）靶向蛋白磷酸酶1调节亚基12A（PPP1R12A），这一作用可抑制丝裂原活化蛋白激酶（MAPK）和PI3K/AKT信号通路的激活，从而控制CCA细胞的存活和转移。此外，miR-455-5p在CCA组织中的表达降低，且与PPP1R12A呈负相关，PPP1R12A基因敲低后的表型模拟了miR-455-5p对CCA细胞的影响。此外，我们证明高良姜素在体外和体内均能抑制CCA生长，这与miR-455-5p的增加和PPP1R12A表达的抑制有关。作为支持，miR-455-5p的过表达消除了高良姜素介导的抗CCA作用。这些发现确立了miR-455-5p在CCA发展中的重要作用，高良姜素可能为抗CCA治疗提供一种潜在的治疗辅助药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c41/8210562/3f1d4c1693bd/jcav12p4710g006.jpg
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