Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis

Abstract

Objective This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism. Methods The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meniscus, followed by measurement of Gm37494, microRNA (miR)-181a-5p, GABRA1 mRNA, and the encoded GABAARα1 protein expression. Thereafter, a cellular model was induced by interleukin-1β (IL-1β) treatment in chondrocytes, followed by ectopic and silencing experiments. Chondrocyte proliferation was detected by CCK-8 and EdU assays, chondrocyte apoptosis by flow cytometry and western blot, and the levels of inflammatory factors by ELISA. The binding of Gm37494 to miR-181a-5p was evaluated by dual-luciferase reporter gene and RIP assays, and that of GABRA1 to miR-181a-5p by dual-luciferase reporter gene and RNA pull-down assays. Results OA patients and mice had decreased GABRA1 mRNA and GABAARα1 protein levels and elevated miR-181a-5p expression in cartilage tissues. Additionally, Gm37494 was poorly expressed in OA mice. Mechanistically, Gm37494 directly bound to and inversely modulated miR-181a-5p that negatively targeted GABRA1. In IL-1β-induced chondrocytes, Gm37494 overexpression enhanced cell proliferation and suppressed cell apoptosis and inflammation, whereas further miR-181a-5p up-regulation or GABRA1 silencing abolished these trends. Conclusions Conclusively, Gm37494 elevated GABRA1 expression by binding to miR-181a-5p, thus ameliorating OA-induced chondrocyte damage.

Role of signal transduction pathways in IL‐1β‐induced apoptosis: Pathological and therapeutic aspects

“…Apart from the currently reported drugs, numerous other biotherapeutic studies have been published. circular RNAs 96 , 97 , 98 and Long noncoding RNAs 99 , 100 , 101 are currently a hot topic of research, and their antiapoptotic mechanisms are not identical to those of traditional signal pathways, pending further in‐depth studies at the molecular level.…”

Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers

“…The aberrant expression of GABA and GABA receptors has been associated with cancer development, metastasis, and suppression of immunosurveillance [ 71 , 74 ]. In this scenario, lncRNAs, as well as miRNAs, may regulate neuronal activity and target GABA receptors [ 59 , 75 , 76 ]. For instance, one recent study examined the role of the lncRNA Gm37494 in the context of osteoarthritis, focusing on its capability to target GABRA1 by binding to miR-181a-5p [ 76 ].…”

“…In this scenario, lncRNAs, as well as miRNAs, may regulate neuronal activity and target GABA receptors [ 59 , 75 , 76 ]. For instance, one recent study examined the role of the lncRNA Gm37494 in the context of osteoarthritis, focusing on its capability to target GABRA1 by binding to miR-181a-5p [ 76 ]. Therefore, it appears plausible, yet remains to be demonstrated, that LINC01087 (and probably other lncRNAs) regulate GABA receptor activity during the formation and progression of specific cancer types.…”

PARP9 knockdown confers protection against chemoresistance and immune escape of breast cancer cells by blocking the PI3K/AKT pathway

“…The gray scale ratio of the corresponding protein band to the GAPDH protein band was regarded as the relative protein level. The experiment was repeated three times to obtain the mean value [25,26].…”