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

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.

Automated summary

miR-141 and miR-200a are significantly downregulated in liver cancer and are closely associated with clinical features. They synergistically inhibit the expression of E-cadherin and vimentin during epithelial-mesenchymal transition by targeting STAT4, influencing the proliferation, migration, and invasion of liver cancer cells. Overexpression of both miRNAs together has stronger effects, while overexpression of STAT4 can reverse their tumor suppressive roles. These findings expand the understanding of the tumor suppressor mechanisms of the miR-200 family and may have implications for using miRNAs in the diagnosis, prognosis, and treatment of liver cancer.