microRNA-206 Suppresses Cholangiocarcinoma Cell Growth and Invasion by Targeting Jumonji AT-Rich Interactive Domain 2.

Abstract

BACKGROUND:

The current study set out to elucidate the specific role of microRNA (miR)-206 in cholangiocarcinoma (CCA) cell biological activities by negatively modulating jumonji AT-rich interactive domain 2 (JARID2).

METHODS:

Firstly, human intrahepatic biliary epithelial cells and CCA cell lines were selected via the analysis of miR-206 and JARID2 expression patterns in CCA by qRT-PCR. Next, the target relation between miR-206 and JARID2 was predicted by Targetscan and validated using dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Subsequently, CCK-8 method, colony formation assay, scratch test, Transwell assay, and western blot analysis were performed to evaluate cancer cell development after the overexpression of miR-206 and/or JARID2, with levels of invasion-related proteins assessed. In addition, xenograft transplantation was also employed to confirm the role of miR-206 in vivo. Lastly, Ki-67 expression pattern was also quantified with immunohistochemistry.

RESULTS:

It was found that miR-206 was poorly expressed and JARID2 was highly expressed in CCA cell lines. Also, miR-206 overexpression brought about a suppressive effect on cancer cell proliferation, migration, and invasion. Furthermore, miR-206 was observed to target JARID2. Meanwhile, JARID2 overexpression promoted cell growth, while simultaneous overexpression of miR-206 and JARID2 impeded malignant cancer progression, indicating that miR-206 overexpression inhibited cell progression via targeting JARID2. Finally, in vivo experimentation illustrated that miR-206 overexpression suppressed tumor growth and weight, and inhibited the expressions of JARID2 N-cadherin, vimentin, and Ki-67.

CONCLUSION:

Altogether, our findings clarified that miR-206 inhibited CCA malignancy by negatively regulating JARID2.

• Authors: Chunying Xie, Zhenxing Huang, Zhaohui Huang, Xue Zhang, Siyuan Lou
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 67 Issue 7 Pg. 2994-3005 (07 2022) ISSN: 1573-2568 [Electronic] United States
• PMID: 34240323 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• JARID2 protein, human
• Ki-67 Antigen
• MIRN206 microRNA, human
• MicroRNAs
• Polycomb Repressive Complex 2

Topics

• Bile Duct Neoplasms (pathology)
• Bile Ducts, Intrahepatic (pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Cholangiocarcinoma (pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Ki-67 Antigen (metabolism)
• MicroRNAs (genetics, metabolism)
• Polycomb Repressive Complex 2 (antagonists & inhibitors)