MicroRNA‑200a and microRNA‑141 have a synergetic effect on the suppression of epithelial‑mesenchymal transition in liver cancer by targeting STAT4

Chen,Shuying; Zhang,Jingjun; Chen,Qiudan; Cheng,Juan; Chen,Xiaotong; Mao,Yinqi; Chen,Wei; Liu,Chenbin; Wu,Han; Lv,Yuan; Lin,Yong

doi:10.3892/ol.2020.12398

MicroRNA‑200a and microRNA‑141 have a synergetic effect on the suppression of epithelial‑mesenchymal transition in liver cancer by targeting STAT4

Authors:
- Shuying Chen
- Jingjun Zhang
- Qiudan Chen
- Juan Cheng
- Xiaotong Chen
- Yinqi Mao
- Wei Chen
- Chenbin Liu
- Han Wu
- Yuan Lv
- Yong Lin
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Affiliations: Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Central Laboratory, Clinical Laboratory, Jingan District Central Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
Published online on: December 20, 2020 https://doi.org/10.3892/ol.2020.12398
Article Number: 137
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs or miRs) are non‑coding small RNAs that target specific messenger RNAs to inhibit protein translation. miR‑200a and miR‑141 function as tumor suppressors by targeting STAT4. These two miRNAs belong to the same family, and their expression is often decreased in various cancer types, but are located on different chromosomes of the human genome. The present study showed that the expression levels of miR‑141 and miR‑200a in serum and cells of liver cancer are significantly downregulated. The expression levels of miR‑141 and miR‑200a are closely associated with clinicopathological features of liver cancer, especially metastasis and invasion. It is first reported that STAT4 is the new common target gene of miR‑141 and miR‑200a. In the present study, miR‑141 and miR‑200a were confirmed to inhibit the expression of E‑cadherin and vimentin synergistically during epithelial‑mesenchymal transition to regulate the proliferation, migration and invasion of liver cancer cells by targeting STAT4. Simultaneous overexpression of miR‑200a and miR‑141 resulted in stronger effects compared with each miRNA alone. In addition, overexpression of STAT4 significantly reversed the tumor suppressive roles of miR‑200a and miR‑141 in liver cancer cells. These findings enrich the tumor suppressor mechanisms of the miR‑200 family, and may also provide new experimental and theoretical basis for the use of miRNAs for early diagnosis, prognosis and thorough treatment of liver cancer.

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