LncRNA SNHG7/miR-34a-5p/SYVN1 axis plays a vital role in proliferation, apoptosis and autophagy in osteoarthritis

Abstract

Background: Osteoarthritis (OA) is one of the most common rheumatic diseases of which clinical symptoms includes swelling, synovitis and inflammatory pain, affect patients' daily life. It was reported that non-coding RNAs play vital roles in OA. However, the regulation mechanism of ncRNA in OA pathogenesis has not been fully elucidated. Methods: The expression of SNHG7, miR-34a-5p and SYVN1 was detected using qRT-PCR in tissues, serum and cells. The protein expression of SYVN1, PCNA, cleavage-caspase 3, beclin1 and LC3 were measured using western blot. The RNA immunoprecipitation (RIP), RNA pulldown, and luciferase reporter assays were used to verify the relationship between SNHG7, miR-34a-5p and SYVN1. The MTT and flow cytometry assay was performed to detected cell proliferation and cell apoptosis respectively. Results: In this study, SNHG7 and SYVN1 expression were down-regulated, but miR-34a-5p was up-regulated in OA tissues and IL-1β treated cells compared with normal tissues and chondrocyte. Functional investigation revealed that up-regulated SNHG7 or down-regulated miR-34a-5p could promote cell proliferation and inhibit cell apoptosis and autophagy in OA cells. More than that, RIP, pulldown and luciferase reporter assay was applied to determine that miR-34a-5p was a target miRNA of SNHG7 and SYVN1 was a target mRNA of miR-34-5p. Rescue experiments showed that overexpression of miR-34a reversed high expression of SNHG7-mediated suppression of apoptosis and autophagy as well as promotion of proliferation, while its knockdown inhibited cell apoptosis and autophagy and promoted cell proliferation which could be impaired by silencing SYVN1. In addition, SNHG7 regulated SYVN1 through sponging miR-34a-5p. Conclusion: SNHG7 sponged miR-34a-5p to affect cell proliferation, apoptosis and autophagy through targeting SYVN1 which provides a novel sight into the pathogenesis of OA.

<p>Long Non-Coding RNA SNHG7 Alleviates Oxygen and Glucose Deprivation/Reoxygenation-Induced Neuronal Injury by Modulating miR-9/SIRT1 Axis in PC12 Cells: Potential Role in Ischemic Stroke</p>

“…Besides, numerous studies have revealed the key role of SNHG7 in many diseases. [11][12][13] SNHG7 can inhibit the high glucoseinduced proliferation and migration of human retinal endothelial cells in DR. 12 SNHG7 promotes cell viability and represses cell apoptosis in osteoarthritis. 13 SNHG7 suppresses cell viability of cardiac fibroblasts in cardiac fibrosis.…”

“…10 Specifically, lncRNA small nucleolar RNA host gene 7 (SNHG7), located on chromosome 9q34.3, has been reported to make imperative impacts on diverse diseases. [11][12][13] SNHG7 suppresses cell viability of cardiac fibroblasts in cardiac fibrosis. 11 SNHG7 can inhibit the high glucose-induced proliferation and migration of human retinal endothelial cells in diabetic retinopathy (DR).…”

“… 12 SNHG7 can promote viability of cartilage cells and suppress apoptosis of cartilage cells in osteoarthritis. 13 However, the role and mechanism of SNHG7 in IS have not been elucidated till now.…”

Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis

“…For example, FOXD2-AS1 induced the proliferation of chondrocytes in OA by sponging miR-27a-3p [ 49 ], lncRNA-CIR regulated the apoptosis of chondrocytes in OA [ 50 ], and overexpression of lncRNA-ROR significantly promoted the viability of OA chondrocytes and regulated the autophagy and apoptosis of chondrocytes through p53 and HIF1 α [ 51 ]. Tian et al [ 52 ] verified that lncRNA SNHG7 expression was downregulated in OA cartilage tissues compared with healthy cartilage tissues and overexpressed lncRNA SNHG7 inhibited cell apoptosis and autophagy and promoted cell proliferation by regulating the miR-34a-5p/SYVN1 axis. However, there were few studies on the mechanism of lncRNAs involved in cartilage or meniscus degeneration in KOA, such as lnc-HLA-DQA1-5, lnc-RP11-127H5.1.1-1, and lnc-RTN2-1.…”

Osteoarthritis year in review: genetics, genomics, epigenetics

“…In OA, the process of autophagy inhibits inflammation and reduces chondrocyte apoptosis and variants in autophagy related genes increase risk of OA [44]. In addition to miR-140-5p and miR-146a, other miR that promoted autophagy in chondrocytes include miR-34a-5p, miR-107, miR-335-5p and miR-let-7e [45][46][47][48]. MicroRNAs that decreased autophagic processes include miR-206, miR-375, miR-411, and miR-449 [49][50][51][52].…”