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LncRNA UCA1 通过调节 CYP1B1 介导的 miR-513a-3p 在人胃癌中的凋亡来增强顺铂耐药性
Authors Cheng H, Sharen G, Wang Z, Zhou J
Received 19 August 2020
Accepted for publication 11 November 2020
Published 14 January 2021 Volume 2021:13 Pages 367—377
DOI https://doi.org/10.2147/CMAR.S277399
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Alexandra R. Fernandes
Background: Chemoresistance contributes to treatment failure of gastric cancer (GC) patients but the molecular mechanism of chemoresistance in GC is still unclear. Long-chain noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1 ) is associated with resistance to chemotherapy drugs.
Methods: We detected the expression of UCA1 in 53 pairs of GC tumor tissue and adjacent normal tissue, human normal gastric mucosa cells (GES-1) and human GC cells (HGC-27, SNU-5, AGS, SGC-7901, and NCI-N87) using RT-qPCR. Small RNA interference technology was used to knock down the expression of UCA1 in gastric cancer cells. CCK8 solution was used to detect cell viability. Flow cytometry was used to detect apoptosis, and Western blotting was used to detect protein expression.
Results: UCA1 was highly expressed in GC tissues and cells, and knockdown of UCA1 increased chemosensitivity to cisplatin by inducing cell apoptosis. Furthermore, UCA1 promoted CYP1B1 expression by binding to miR-513a-3p in human GC cells in vitro, and UCA1 /CYP1B1 expression was negatively related to miR-513a-3p expression, while UCA1 expression was positively related to CYP1B1 expression in human GC tissues. Moreover, overexpression of miR-513a-3p or knockdown of CYP1B1 increased chemosensitivity to cisplatin, and knockdown of miR-513a-3p or overexpression of CYP1B1 decreased chemosensitivity to cisplatin by inducing cell apoptosis in human GC cells. Importantly, overexpression of CYP1B1 reduced chemosensitivity to cisplatin which increased by knockdown of UCA1 , and knockdown of CYP1B1 increased chemosensitivity to cisplatin which decreased by knockdown of miR-513a-3p in human GC cells.
Conclusion: The lncRNA UCA1 /miR-513a-3p /CYP1B1 axis regulates cisplatin resistance in human GC cells; hence, it is a potential target for treating chemoresistance in GC.
Keywords: gastric cancer, urothelial cancer associated 1, chemoresistance