SNHG12 promotes chondrocyte autophagy by blocking he mTOR-primary cilia-mTOR loop via activating the miR-181a-5p/miR-138-5p-INPP5E axis

Abstract Chondrocytes are the only cell type found in normal cartilage. In this study, RT-PCR results showed that silencing INPP5E inhibited the mRNA expressions of IFT88, Beclin1, MAP1LC3A, MAP1LC3B, PI3K, Akt, mTOR, COL2A1 and CCND1 in chondrocytes. WB results showed that silencing INPP5E inhibited the protein expressions of IFT88, Beclin1, LC3 I, LC3 II, phosphorylated(p)-PI3K, p-Akt, p-mTOR, collagen II and cyclin D1 in chondrocytes. Immunofluorescence results showed that silencing INPP5E inhibited acetylated α-tubulin and LC3 II in chondrocytes. RT-PCR, WB and dual luciferase assay showed that SNHG12 promoted the expression of INPP5E by inhibiting hsa-miR-181a-5p or hsa-miR-138-5p. Functional recovery experiments show that SNHG12 regulated the expression of IFT88, Beclin1, LC3 I, LC3 II, p-PI3K, p-Akt, p-mTOR, collagen II and cyclin D1 via hsa-miR-181a-5p/hsa-miR-138-5p-INPP5E axis in chondrocytes. Our results provide a theoretical basis for the treatment of patients with cartilage abnormalities related diseases.