Long noncoding RNA UCA1 inhibits epirubicin-induced apoptosis by activating PPARα-mediated lipid metabolism.

Autor: Sun S; Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University and the Key Clinical Laboratory of Henan Province, Zhengzhou, China., Li H; Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China., Liu S; Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou, China., Xie X; Shaanxi Center for Clinical Laboratory, Shaanxi Provincial People's Hospital, Xi'an, China., Zhai W; Department of Medical Genetics, Northwest Women's and Children's Hospital, Xi'an, China., Pan J; Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University and the Key Clinical Laboratory of Henan Province, Zhengzhou, China. Electronic address: pan696@163.com.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2024 Oct 01; Vol. 442 (2), pp. 114271. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1016/j.yexcr.2024.114271
Abstrakt: Metabolic reprogramming is a hallmark of cancer, and abnormal lipid metabolism is associated with drug resistance in bladder cancer cells. The long noncoding RNA (lncRNA) UCA1 is overexpressed in bladder cancer, but its functional contribution to lipid metabolism remains uncharacterized. In this study, we demonstrated that lncRNA UCA1 inhibits epirubicin-induced cell apoptosis by supporting abnormal lipid metabolism in bladder cancer cells. Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPARα mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARα and downstream p-AKT/p-GSK-3β/β-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRα to the lncRNA UCA1 promoter. These findings were verified in a mouse xenograft model and are consistent with the expression patterns in human bladder cancer patients. Overall, these findings establish the role of lncRNA UCA1 in lipid metabolism and bladder cancer cell resistance to epirubicin, suggesting that lncRNA UCA1 may serve as a candidate target for enhancing bladder cancer chemotherapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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