miR-144-5p and miR-451a Inhibit the Growth of Cholangiocarcinoma Cells Through Decreasing the Expression of ST8SIA4

Wan Fu; Guangcai Yu; Junnan Liang; Pan Fan; Keshuai Dong; Bixiang Zhang; Xiaoping Chen; Hong Zhu; Liang Chu

doi:10.3389/fonc.2020.563486

miR-144-5p and miR-451a Inhibit the Growth of Cholangiocarcinoma Cells Through Decreasing the Expression of ST8SIA4

Front Oncol. 2021 Jan 14:10:563486. doi: 10.3389/fonc.2020.563486. eCollection 2020.

Authors

Wan Fu^{1

2}, Guangcai Yu³, Junnan Liang^{1

2}, Pan Fan^{1

2}, Keshuai Dong^{1

2}, Bixiang Zhang^{1

2}, Xiaoping Chen^{1

2}, Hong Zhu⁴, Liang Chu^{1

2}

Affiliations

¹ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Provincial Key Laboratory of Hepatobiliary and Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Abstract

Accumulating evidences indicate that non-coding RNAs play crucial roles in the progression of an extensive range of carcinomas. This study aimed to investigate the action mechanism of miR-144-5p and miR-451a in cholangiocarcinoma. We found that miR-144-5p and miR-451a were significantly decreased in cholangiocarcinoma patient samples compared to the adjacent normal bile duct samples. The downregulation of these two miRNAs was correlated with a more advanced disease state of cholangiocarcinoma patients. Overexpression of miR-144-5p and miR-451a suppressed the proliferation, invasion and migration of cholangiocarcinoma cells in vitro and inhibited xenograft tumor growth. Knockdown of these two miRNAs had the opposite effects. miR-144-5p and miR-451a regulated the expression of ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4), and presented a correlation with ST8SIA4 in patient samples. Overexpression of ST8SIA4 promoted the proliferation, invasion and migration of cholangiocarcinoma cells, and the changes were reversed by upregulating the expression of miR-144-5p and miR-451a. Our findings indicated that miR-144-5p and miR-451a displayed a tumor suppressor role through decreasing the expression of ST8SIA4 in cholangiocarcinoma.

Keywords: ST8SIA4; cholangiocarcinoma; miR-144-5p; miR-451a; tumor suppressor.