All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members

作者全名："Cui, Jiejie; Gong, Mengjia; Fang, Shuyu; Hu, Chaoqun; Wang, Yi; Zhang, Jingfang; Tang, Ni; He, Yun"

作者地址："[Cui, Jiejie; Gong, Mengjia; Fang, Shuyu; Hu, Chaoqun; Wang, Yi; Tang, Ni; He, Yun] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders,China In, Key Lab Child Dev & Disorders,Dept Pediat Surg, Chongqing Key Lab Pediat,Childrens Hosp,Minist Ed, Chongqing 401122, Peoples R China; [Cui, Jiejie; Zhang, Jingfang] Puyang Peoples Hosp, Puyang 457000, Henan, Peoples R China"

通信作者："He, Y (corresponding author), Chongqing Med Univ, Dept Pediat Surg, Childrens Hosp, Room 905,Bldg 7,136 Zhongshan Er Rd, Chongqing 400014, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000661449300011

JCR分区：Q1

影响因子：6.8

年份：2021

卷号：8

期号：4

开始页：509

结束页：520

文献类型：Article

关键词：All-trans retinoic acid; Differentiation; Epithelial-mesenchymal transition; Hepatocellular carcinoma cells; microRNA 200

摘要："As a potential chemo-therapeutic agent, all-trans retinoic acid (ATRA) can significantly reverse epithelial-me senchymal transition (EMT) of hepal-6 hepatocarcinoma cell line in vitro, but the mechanism is unclear. The expression profile of microRNA-200 (miR-200) families is different in hepatocellular carcinoma. In this study, we found that ATRA treatment could up-regulate the expression of miR-200 a-3p, 200 c-3p, and 1 41-3p, which were involved in ATRA regulated proliferation and apoptosis of hepal-6 cell, but not colony formation. Meanwhile, miR-200a-3p, 200c-3p, and 141-3p could recovery ATRA inhibited migration and invasion abilities of hepal-6 cells at various levels. miR-200a-3p and 200c-3p prevented ATRA from inducing the differentiation and hepatic functions of hepal-6 cells. Antagomir specific for miR-200 a-3p and 200c-3p down-regulated the expression of CK18, but only miR-200a-3p antagomir played prominent role in regulating the expression of these mesenchymal markers, N-Cadherin, Snail and Twist. The transcriptional activities of 8 transcription factors were up-regulated and 35 transcription factors were down-regulated by ATRA. Compared with ATRA group, inhibition of miR-200a-3p, 200c-3p, and 141-3p significantly strengthened the expression of Fra1 /Jun (AP1), Ets1 /PEA3, Brn3, and Zeb1 / AREB6 at varying degrees. Therefore, this result suggested that ATRA may suppress EMT through down-regulating miR-200a-3p, 200c-3p and 141-3 p related transcription factors. miR-200 and their downstream genes might be the potentially specific targets for the treatment of hepatocarcinoma. Copyright (C) 2020, Chongqing Medical University. Production and hosting by Elsevier B.V."

基金机构："Natural Science Foundation of Chongqing CityNatural Science Foundation of Chongqing [cstc2018jcyjAX0111, csct2016jcyjA0228]; Program for Innovation Team Building at Institutions of Higher Education in Chongqin [CXTDX201601015]"

基金资助正文："The reported work was supported by a research grant from the Natural Science Foundation of Chongqing City [grant numbers cstc2018jcyjAX0111 to YH, csct2016jcyjA0228 to YB] and the Program for Innovation Team Building at Institutions of Higher Education in Chongqin [grant number CXTDX201601015 to NT]."