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miR-144-5p和miR-451a通过降低ST8SIA4的表达来抑制胆管癌细胞的生长。

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

作者信息

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

机构信息

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hubei Provincial Key Laboratory of Hepatobiliary and Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

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

DOI:10.3389/fonc.2020.563486
PMID:33520692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7841262/
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 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 (), 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.

摘要

越来越多的证据表明，非编码RNA在多种癌症的进展中起着关键作用。本研究旨在探讨miR-144-5p和miR-451a在胆管癌中的作用机制。我们发现，与相邻正常胆管样本相比，胆管癌患者样本中miR-144-5p和miR-451a显著降低。这两种miRNA的下调与胆管癌患者更晚期的疾病状态相关。miR-144-5p和miR-451a的过表达抑制了胆管癌细胞的增殖、侵袭和迁移，并抑制了异种移植肿瘤的生长。敲低这两种miRNA则产生相反的效果。miR-144-5p和miR-451a调节ST8α-N-乙酰神经氨酸α-2,8-唾液酸转移酶4（ST8SIA4）的表达，并且在患者样本中与ST8SIA4呈相关性。ST8SIA4的过表达促进了胆管癌细胞的增殖、侵袭和迁移，而上调miR-144-5p和miR-451a的表达可逆转这些变化。我们的研究结果表明，miR-144-5p和miR-451a通过降低ST8SIA4在胆管癌中的表达发挥肿瘤抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e94/7841262/57ca95f67231/fonc-10-563486-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e94/7841262/57ca95f67231/fonc-10-563486-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e94/7841262/0427dca953d9/fonc-10-563486-g001.jpg
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