1. SOX4-activated lncRNA MCM3AP-AS1 aggravates osteoarthritis progression by modulating miR-149-5p/Notch1 signaling
- Author
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Fei Xu, Qun-Fang Hu, Jia Li, Chang-Jiang Shi, Jin-Wei Luo, Wei-Chao Tian, and Li-Wei Pan
- Subjects
Immunology ,Intracellular Signaling Peptides and Proteins ,Apoptosis ,Hematology ,Biochemistry ,Rats ,SOXC Transcription Factors ,MicroRNAs ,Chondrocytes ,Acetyltransferases ,Osteoarthritis ,Animals ,Humans ,Immunology and Allergy ,RNA, Long Noncoding ,Receptor, Notch1 ,Molecular Biology ,Cell Proliferation ,Signal Transduction - Abstract
To clarify the expression and underlying network of long non-coding RNA (lncRNA) MCM3AP-AS1 in osteoarthritis (OA).Human articular cartilage samples, OA model rats and IL-1β-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. HE staining was used to detect the pathological changes of cartilage.MCM3AP-AS1 was upregulated in OA patients and IL-1β-induced chondrocytes. Knockdown of MCM3AP-AS1 enhanced autophagy, while alleviated ECM degradation and cartilage injury. Mechanistically, overexpression 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 weakened the biological impacts of MCM3AP-AS1 silencing.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.
- Published
- 2022
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