LncRNA DNM3OS promotes proliferation and inhibits apoptosis through modulating IGF1 expression by sponging MiR-126 in CHON-001 cells

Abstract

Background: As a degenerative disease, osteoarthritis (OA) greatly affects aged population. The human chondrocyte cell line CHON-001, derived from normal human articular cartilage, has been widely used in vitro in osteoarthritis models. In order to better understand the underlying mechanism of OA pathogenesis, this study was conducted to explore the effects of LncRNA dynamin 3 opposite strand (DNM3OS) on CHON-001 cells. Methods: The expression levels of and correlation between DNM3OS and miR-126 that derived from OA and non-OA tissues were determined by quantitative real time (qRT)-PCR and Spearman's correlation analysis. Cell viability, clone, migration, invasion and apoptosis were respectively determined by cell counting kit-8, colony formation, wound healing assay, transwell and flow cytometry. The target genes were predicted by starbase V2 and targetscan 7.2 and confirmed by luciferase reporter assay. The expressions of apoptosis-related factors were detected by Western blot. Results: The expression of DNM3OS was down-regulated in OA patients. Functional assays demonstrated that ectopic expression of DNM3OS promoted the proliferation and inhibited apoptosis of CHON-001 cells, and that knocking down DNM3OS suppressed cell proliferation and induced apoptosis. Mechanistic investigation revealed that DNM3OS physically bound to the promoter of miR-126 and suppressed miR-126 expression. Decreased expression of DNM3OS was negatively correlated with miR-126 in OA patients. Furthermore, the effects of siDNM3OS on inhibiting cell proliferation and promoting apoptosis were partially reversed by miR-126 inhibitor. Meanwhile, type insulin-like growth factor-1 (IGF1) was identified as a target gene for miR-126 and was negatively associated with the miR-126 expression. Overexpressed IGF1 restored the effects of miR-126 mimic in suppressing cell proliferation and promoting apoptosis. Conclusion: Our results showed that DNM3OS could affect the CHON-001 cell proliferation and apoptosis by regulating IGF1 by sponging miR-126.

lncRNA SNHG16 promotes the occurrence of osteoarthritis by sponging miR‑373‑3p

“…As a ncRNA subclass, long ncRNAs (lncRNAs) are >200 nucleotides in length, and display improved tissue and cell specificity compared with coding RNAs. lncRNAs are differentially expressed in different cells, tissues and developmental stages, and are associated with the occurrence and development of various diseases, including OA and malignancies ( 7 – 10 ). Moreover, it has been confirmed that enriched lncRNAs in the cytoplasm typically participate in post-transcriptional modification by binding to microRNAs (miRNAs/miRs) or mRNAs ( 8 ).…”

Up-regulation of long non-coding RNA CYTOR induced by icariin promotes the viability and inhibits the apoptosis of chondrocytes

“…In recent years, accumulating studies indicate that lncRNA is involved in the development of OA and is related to chondrocyte viability and apoptosis. For example, lncRNA DNM3OS can adsorb miR-126 as a molecular sponge to regulate insulin-like growth factor 1 to promote chondrocyte proliferation and inhibit apoptosis [14]; lncRNA SNHG1 can alleviate IL-1β-induced injury of chondrocytes by inhibiting miR-16-5p-mediated p38 MAPK and NF-κB signaling pathways [11]. CYTOR, also known as LINC00152, is a lncRNA with a length of 828 nucleotides and expressed abnormally in many cancers, such as lung cancer, stomach cancer, colon cancer, etc.…”

Integrated Analysis of Long Non-Coding RNAs and mRNAs Associated With Malignant Transformation of Gastrointestinal Stromal Tumors

“…Mechanistic investigations revealed that DNM3OS upregulates IGF1 expression to promote proliferation and inhibit apoptosis of CHON-001 cells by sponging miR-126 [44]. Another study suggested that DNM3OS promotes TGFβ1-induced transformation of prostate stromal cells into myo broblasts via miR-29a/29b/COL3A1 and miR-361/TGFβ1 Axes [45].…”