MiR-23b-3p suppresses epithelial-mesenchymal transition, migration, and invasion of hepatocellular carcinoma cells by targeting c-MET
Na Ri Park,
Jung Hoon Cha,
Pil Soo Sung,
Jeong Won Jang,
Jong Young Choi,
Seung Kew Yoon,
Si Hyun Bae
Affiliations
Na Ri Park
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea
Jung Hoon Cha
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea
Pil Soo Sung
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, 06591, Republic of Korea; Corresponding author.
Jeong Won Jang
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, 06591, Republic of Korea
Jong Young Choi
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, 06591, Republic of Korea
Seung Kew Yoon
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, 06591, Republic of Korea
Si Hyun Bae
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, 03382, Republic of Korea; Corresponding author.
Background: Aberrant expression of c-MET is known to be associated with tumor recurrence and metastasis by promoting cell proliferation, epithelial-mesenchymal transition (EMT), and migration in hepatocellular carcinoma (HCC). Recently, miR-23b-3p has been identified as a tumor suppressor, but detailed role of miR-23b-3p in HCC is still unclear. Our study aimed to investigate how miR-23b-3p is associated with the malignant potential of HCC cells. Methods: HCC tissues and their adjacent non-tumor tissues were acquired from 30 patients with HCC. Expression of EMT- or stemness-related genes were examined in the two HCC cell lines. Migration of HCC cells was analyzed using transwell and wound healing assays. Results: c-MET was overexpressed in HCC tissues compared to the adjacent non-tumor tissues. c-MET knockdown inhibited EMT and reduced migration and invasion of HCC cells. Furthermore, c-MET was a target of miR-23b-3p, and miR-23b-3p expression was decreased in HCC tissues compared to non-tumor tissues. Treatment of miR-23b-3p inhibitor in HCC cells promoted EMT, cell migration, and invasion. In contrast, miR-23b-3p overexpression suppressed EMT, cell migration, and invasion, concomitantly reducing c-MET expression. Transfection of miR-23b-3p inhibitor with concomitant c-MET knockdown mitigated the effects of miR-23b-3p inhibitor on EMT in HCC cells. In addition, transforming growth factor beta1 (TGF-β1) stimulation after miR-23b-3p overexpression induced neither the mesenchymal phenotype nor migratory property of HCC cells. Conclusion: In this study, we confirmed that miR-23b-3p downregulation significantly increased EMT, migration, and invasion of HCC cells. In addition, c-MET was confirmed to be a target of miR-23b-3p in HCC cells and regulated the functional effects of miR-23b-3p. These results suggest that miR-23b-3p can be used as a prognostic biomarker and candidate target for HCC treatment.
