Long non-coding RNA KCNQ1OT1 promotes cell viability and migration as well as inhibiting degradation of CHON-001 cells by regulating miR-126-5p/TRPS1 axis

Abstract

Background Osteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells. Methods Relative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p. Results Relative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells. Conclusions Overexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

“…KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and HOXA distal transcript antisense RNA (HOTTIP) have also become a focus of research in recent years. Wang et al [ 112 ] found that the increased level of expression of KCNQ1OT1 enhanced the viability and migratory capacity of CHON-001 cells and inhibited ECM degradation. It is possible that overexpression of KCNQ1OT1 exerted these effects by sponging miR-126-5p to target transcriptional repressor GATA binding 1 (TRPS1).…”

LncRNA PCBP1-AS1 induces osteoporosis by sponging miR-126-5p/PAK2 axis

“… 16 - 18 For instance, lncRNA recombinant Thymopoietin (TMPO-AS-1) causes stomach cancer to grow more quickly by upregulating BRCA1-BRCA2-containing complex (BRCC3) and sponging miR-126-5p. 19 Wang and Liu 20 demonstrated the relationship of the miR-126-5p/transcriptional repressor GATA binding 1 (TRPS1) axis regulation by lncRNA KCNQ1OT1 to the development of osteoarthritis. Other evidence demonstrated that miR-126-5p sponged by PCBP1-AS1 can target group I Pak family member p21-activated kinase 2 (PAK2).…”