SOX4-activated lncRNA MCM3AP-AS1 aggravates osteoarthritis progression by modulating miR-149-5p/Notch1 signaling

Objective: To clarify the expression and underlying network of long non-coding RNA (lncRNA) MCM3AP-AS1 in osteoarthritis (OA). Methods: Human articular cartilage samples, OA model rats and IL-1 beta-treated C28/I2 cells were used in this study. The expression changes of genes and proteins were assessed by real-time quantitative PCR (qRT-PCR) and western blot. Cell viability, apoptosis, autophagy and extracellular matrix (ECM) degradation were assessed by Cell Counting Kit-8 (CCK-8), immunohistochemistry (IHC), flow cytometry, immunofluorescence and western blot assays, respectively. Molecule interactions were validated by dual luciferase and Chromatin immunoprecipitation (ChIP) assays. H&E staining was used to detect the pathological changes of cartilage. Results: MCM3AP-AS1 was upregulated in OA patients and IL-1 beta-induced chondrocytes. Knockdown of MCM3APAS1 enhanced autophagy, while alleviated ECM degradation and cartilage injury. Mechanistically, over expression of SOX4 boosted the transcription of MCM3AP-AS1. Moreover, MCM3AP-AS1 functioned as a molecular sponge or epigenetic regulator of miR-149-5p to facilitate Notch1 expression. Functional rescue experiments showed that either inhibition of miR-149-5p nor ectopic expression of Notch1 dramatically weak-ened the biological impacts of MCM3AP-AS1 silencing. Conclusion: These finding demonstrated that SOX4-activated MCM3AP-AS1 aggravated OA progression by modulating autophagy and ECM degradation via targeting miR-149-5p/Notch1 axis. These data supported that inhibition of MCM3AP-AS1 might be a potential treatment strategy of OA.

Automated summary

In this study, the expression and underlying network of long non-coding RNA (lncRNA) MCM3AP-AS1 in osteoarthritis (OA) were investigated. The results showed that MCM3AP-AS1 was upregulated in OA patients and IL-1 beta-induced chondrocytes. Knockdown of MCM3APAS1 enhanced autophagy, while alleviating extracellular matrix (ECM) degradation and cartilage injury. Mechanistically, MCM3AP-AS1 acted as a molecular sponge or epigenetic regulator of miR-149-5p to facilitate Notch1 expression. Inhibition of MCM3AP-AS1 might be a potential treatment strategy of OA.