All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members
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All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members
Genes & DiseasesVol. 8, Issue 4, (2021)
作者机构:
1. Department of Pediatric Surgery, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University,Chongqing,PR China,401122
Jiejie Cui, Mengjia Gong, Shuyu Fang, et al. All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members. [J]. Genes & Diseases 8(4).(2021)
DOI:
Jiejie Cui, Mengjia Gong, Shuyu Fang, et al. All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members. [J]. Genes & Diseases 8(4).(2021) DOI: 10.1016/j.gendis.2019.12.012.
All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members
摘要
Abstract
a potential chemo-therapeutic agent
all-trans retinoic acid (ATRA) can significantly reverse epithelial-mesenchymal 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-200a-3p
200c-3p
and 141-3p
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-200a-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 141-3p related transcription factors. miR-200 and their downstream genes might be the potentially specific targets for the treatment of hepatocarcinoma.
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