Long non-coding RNA GAS5 aggravate renal epithelial cell apoptosis in cisplatin-induced AKI by regulating miR-205-5p

Abstract

Introduction: The present study focuses on the interaction between long non-coding RNA GAS5 and microRNA-205-5p and their roles in cisplatin-induced acute kidney injury. Methods: Human kidney tubular cells (HK-2) were used to simulate acute renal injury induced by cisplatin with the consequent fluctuating expression levels of GAS5 and MIR-205-5p being determined respectively. Furthermore, the modulating effects of miR-205-5p and GAS5 in cisplatin-induced apoptosis of renal tubular epithelial cells and the possible binding sites between them were evaluated. Results: The results depicted that the expression of GAS5 was significantly up-regulated after AKI induced by cisplatin, while inhibiting the increase of expression would alleviate the apoptotic-promoting effect of cisplatin on renal tubular epithelial cells. MIR-205-5p is negatively regulated by GAS5, thus down-regulation of GAS5 will consequently elevate the expression of miR-205-5p and further alleviate the damage of HK-2 cells induced by cisplatin. Conclusions: In conclusion, in cisplatin-induced AKI, the expression of GAS5 was increased and consequently inhibited that of miR-205-5p by direct binding, which eventually aggravate the renal tubular epithelial injury, indicating their potential of being important diagnostic markers and therapeutic targets in the treatment of cisplatin-induced AKI.

MicroRNAs Involved in Intrinsic Apoptotic Pathway during Cisplatin-Induced Nephrotoxicity: Potential Use of Natural Products against DDP-Induced Apoptosis

“…Another study demonstrated that HK-2 cells stimulated with DDP showed that the downregulation of miR-205-5p promoted cell apoptosis, observed by an enhanced caspase-3 activity and apoptosis rate of in vitro cultured cells. However, enhancing miR-205-5p expression suppressed apoptotic rate [ 72 ]. The levels of miR-144-5p were also downregulated in DDP-stimulated HK-2 cells, and the expression levels of apoptosis-related proteins showed that enhancing miR-144-5p expression was able to increase the expression levels of caspase-3/-9, and Bax, and to decrease the expression levels of Bcl-2, by regulating PKM2 expression [ 71 ].…”

Epigenetic Mechanisms Involved in Cisplatin-Induced Nephrotoxicity: An Update

“…Thus, during CDDP-induced damage, lncRNA LRNA9884 increases NF-κB-mediated inflammatory cytokines, especially MIF [ 103 ]. Likewise, lncRNA GAS5 can increase CDDP-induced apoptosis of HK-2 cells by modulating miR-205-5p [ 104 ].…”