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Dysregulated lncRNAs in Cisplatin-Induced Nephrotoxicity and Their Association with Apoptosis and Autophagy: An Exploratory In Vitro Study

Year: 2025

Type: article

Abstract: Cisplatin is a widely used chemotherapeutic agent, but its clinical application is limited by nephrotoxicity. Conventional renal markers lack sensitivity for early cisplatin nephrotoxicity while long non-coding RNAs (lncRNAs) display cisplatin-responsive changes with exploratory value. The present study aimed to explore the differential expression of eight lncRNAs on in vitro model of cisplatin-induced nephrotoxicity. Human kidney cell lines HEK-293 and HK-2 were exposed to increasing concentrations of cisplatin for 24 h. Cell viability was determined by colorimetric assays to ascertain the concentrations resulting in 25% (IC25), 50% (IC50), and 75% (IC75) cell death (inhibitory concentration). Apoptotic and autophagy-related proteins were analyzed by Western blot, and reverse transcription–polymerase chain reaction was employed to evaluate the expression of the lncRNAs. Cisplatin-induced cell death with IC25, IC50, and IC75 values of 8.8, 15.43 and 27 μM for HEK-293 cells, and 8.1, 13.57, and 22.8 μM for HK-2 cells. Protein analysis showed an increase in cleaved caspase-9, reduction of caspase-3 and increased LC3-II/LC3-I ratio, with no changes in caspase 7 and Beclin-1. The lncRNAs UCA1, XLOC_032768, HOTAIR, LINC-ROR, and PRNCR1 were downregulated, whereas OIP5-AS1 was upregulated; in contrast, GAS5 and PVT1 remained unchanged. In conclusion, this exploratory in vitro study identifies cisplatin-responsive dysregulation of lncRNAs in human renal cells and delineates their associations with apoptosis and autophagy.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms262211201