LINC02288 promotes chondrocyte apoptosis and inflammation through miR‐374a‐3p targeting RTN3

Abstract

Background: Dysregulation of long non-coding RNAs (lncRNAs) is related to the occurrence of osteoarthritis (OA). In the present study, we explored the role of LINC02288 and its regulatory mechanism in OA development.Methods: GSE113825 was obtained from Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed lncRNAs in OA. Gene enrichment analyses and Kyoto Encyclopedia of Genes and Genomes biological process analysis were performed through Metascape (http://metascape.org/gp). The interactions among LINC02288, miR-374a-3p and RTN3 were determined using RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays. Chondrocyte apoptosis was examined using flow cytometry. Western blot assays were conducted to assess the pro-apoptotic and anti-apoptotic markers.Results: We identified a total of 4,491 differentially expressed lncRNAs. We focused on LINC02288 as the top-ranked up-regulated lncRNA in OA as indicated by a significant p-value. LINC02288 was significantly up-regulated, which was further verified by a real-time polymerase chain reaction. Down-regulation of LINC02288 significantly reduced the apoptosis of OA chondrocytes induced by interleukin-1β and the production of pro-inflammatory cytokines. These effects were further verified in an OA rat model. An RIP assay and dual luciferase assay further confirmed that LINC02288 served as a sponge of miR-374a-3p. Moreover, the overexpression of RTN3 could partially reverse the effects of LINC02288 knockdown, mediating inhibitory effects on chondrocyte apoptosis and the inflammatory response. Down-regulation of LINC02288 alleviated OA development in an in vivo OA animal model. Conclusions:Our findings indicate that LINC02288 contributes to OA progression by targeting the miR-374a-3p/RTN3 axis, which might provide a promising molecular therapy strategy for OA.

Long noncoding RNA Kcnq1ot1 prompts lipopolysaccharide-induced acute lung injury by microRNA-7a-5p/Rtn3 axis

“…Manipulated overexpression of Rtn3 deteriorated ALI in mice independently, whereas downregulating Rtn3 reduced the effect of miR-7a-5p silencing on mice with ALI. Regarding the biological functions of Rtn3, a study report on osteoarthritis has offered evidence that Rtn3 augments apoptosis and inflammatory response of chondrocytes [ 16 ]. Besides, in the setting of ischemia/reperfusion injury, the abnormal elevation of Rtn3 expression is an active stimuli for cardiomyocyte apoptosis [ 36 ].…”

“…Of a member of Rnt, Rtn3 was found to have a potential targeting relation with miR-7a-5p online. Definitely, Fu et al have profiled the pro-inflammatory property of Rtn3 in osteoarthritis [ 16 ]. Till now, little few relevant documents have discovered the relative mechanism underlying ALI with attention on Kcnq1ot1-mediated miR-7a-5p/Rtn3 axis.…”

RNA-Seq Reveals the mRNAs, miRNAs, and lncRNAs Expression Profile of Knee Joint Synovial Tissue in Osteoarthritis Patients

“…Similarly, LINC02288 expression was significantly upregulated in a rat model of OA. LINC02288 knockdown reduced IL-1β-induced apoptosis and proinflammatory cytokine production in OA chondrocytes [ 41 ]. The lncRNA LOC101928134 was highly expressed in the synovial tissue of OA rats, regulated IFNA1 expression, and inhibited the JAK/STAT signaling pathway.…”

Circ_0043947 contributes to interleukin 1β-induced injury in chondrocytes by sponging miR-671-5p to up-regulate RTN3 expression in osteoarthritis pathology

“…Through starbase bioinformatics database, we found that the 3′UTR of reticulon 3 (RTN3) was complementary with miR-671-5p. Fu et al demonstrated that LINC02288 promotes the apoptosis and inflammatory response of chondrocytes partly by up-regulating RTN3 via absorbing miR-374a-3p [20]. In this study, we analyzed the target relationship between RTN3 and miR-671-5p and further explored their functional association in OA pathology.…”