All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members
| Autor: | Shuyu Fang, Yi Wang, Chaoqun Hu, Mengjia Gong, Jiejie Cui, Jing-Fang Zhang, Yun Feng He, Ni Tang |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Medicine (General) Retinoic acid QH426-470 Biochemistry 03 medical and health sciences chemistry.chemical_compound R5-920 0302 clinical medicine ETS1 Full Length Article Genetics Antagomir Epithelial–mesenchymal transition Molecular Biology Transcription factor microRNA 200 Genetics (clinical) Hepatocellular carcinoma cells All-trans retinoic acid Cell Biology AP-1 transcription factor 030104 developmental biology chemistry Apoptosis Cell culture Differentiation 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Genes & Diseases Genes and Diseases, Vol 8, Iss 4, Pp 509-520 (2021) |
| ISSN: | 2352-3042 |
| Popis: | As 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. |
| Databáze: | OpenAIRE |
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