Research Paper|Volume 14, Issue 1|pp 509—525

PSMA3-AS1 induced by transcription factor PAX5 promotes cholangiocarcinoma proliferation, migration and invasion by sponging miR-376a-3p to up-regulate LAMC1

Dongsheng Sun¹, Fujun Li², Lang Liu¹, Shaobo Yu¹, Haicun Wang¹, Xin Gao¹, Guanglin Liu¹, Yuqiao Zhao¹, Gongcai Qiu¹, Xingming Jiang¹

¹Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
²Department of General Surgery, South China Hospital, Health Science Center, Shenzhen University, Shenzhen 518116, China

* Equal contribution

Received: September 15, 2021Accepted: December 29, 2021Published: January 12, 2022

https://doi.org/10.18632/aging.203828

Copyright: © 2022 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long noncoding RNAs (lncRNAs) have been reported to exhibit a crucial regulatory role in tumor progression, including cholangiocarcinoma (CCA). As a promising lncRNA, proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1) is involved in development of various tumors. However, the role and function of PSMA3-AS1 in CCA remain unclear. The aim of this study is to examine the expression, function, mechanism, and clinical significance of PSMA3-AS1 in CCA development. By TCGA database analysis, we found that PSMA3-AS1 was overexpressed in CCA. Consistent with the TCGA analysis, PSMA3-AS1 was significantly overexpressed in CCA tissues and cells by RT-qPCR. Upregulated PSMA3-AS1 was related to lymph node invasion, advanced TNM stage and poor survival, and was an independent risk factor of prognosis for CCA patients. Functionally, CCK-8, EdU and colony formation assays confirmed that upregulated PSMA3-AS1 promoted CCA cell proliferation, whereas downregulated PSMA3-AS1 inhibited proliferation. This result was further confirmed by subcutaneous tumor formation in nude mice. Wound healing and transwell assays confirmed that increased PSMA3-AS1 promoted CCA cell migration and invasion, whereas decreased PSMA3-AS1 inhibited these biological phenotypes. In addition, PSMA3-AS1 promoted the EMT process of CCA by downregulating E-cadherin and upregulating N-cadherin and vimentin. Mechanistically, transcription factor PAX5 bound to the promoter region of PSMA3-AS1 and promoted its transcription. Simultaneously, PSMA3-AS1 primarily localized in the cytoplasm could competitively bind miR-376a-3p to upregulate LAMC1, thereby accelerating CCA progression. This study uncovers that PSMA3-AS1 functions as a cancer-promoting gene in CCA, and PAX5/PSMA3-AS1/miR-376a-3p/LAMC1 axis plays a vital role in CCA development.