Circular RNA CircACAP2 regulates temporomandibular joint osteoarthritis via miR-21-5p/PLAG1 axis.

OBJECTIVES: The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR-21-5p may participate in the TMJOA development and the interaction between circRNA-ACAP2 (CircACAP2) and miR-21-5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA. MATERIALS AND METHODS: The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR-21-5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual-luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model. RESULTS: The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR-21-5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models. CONCLUSIONS: The present study unveiled that CircACAP2/miR-21-5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA.

CircRNA_ACAP2 Suppresses EMT in Head and Neck Squamous Cell Carcinoma by Targeting the miR-21-5p/STAT3 Signaling Axis.

Circular RNAs (circRNAs) contain microRNA (miRNA)-specific binding sites and can function as miRNA sponges to regulate gene expression by suppressing the inhibitory effect of miRNAs on their target genes. MiR-21-5p has been reported to be involved in the development of head and neck squamous cell carcinoma (HNSCC) and plays an important role in the activation of epithelial-mesenchymal transition (EMT). However, the upstream regulatory mechanism and downstream targets of miR-21-5p in tumor cells remain unknown. CircRNA_ACAP2 inhibits the function of miR-21-5p by binding to its specific binding sites in HNSCC cells. Overexpression of CircRNA_ACAP2 inhibits the proliferation and migration of HNSCC cells, while downregulation of CircRNA_ACAP2 has the opposite effect. STAT3 is a direct target gene of miR-21-5p and a transcription factor of ZEB1. We demonstrate that CircRNA_ACAP2 functions as a tumor suppressor gene in HNSCC and that its function is regulated via the miR-21-5p/STAT3 signaling axis.

[Effect of p38 mitogen-activated protein kinase signaling pathway during stretch-induced differentiation process of C2C12 myoblasts].

OBJECTIVE: To investigate the effect of cyclic stretch on p38 mitogen-activated protein kinase (p38MAPK) signaling pathway during stretch-induced differentiation process of C2C12 myoblasts. METHODS: C2C12 cells were seeded on Bio Flex 6-well plates, and cells were subsequently subjected to cyclic stretch at an optimal magnitude (10%) and frequency (0.5 Hz). The effects of cyclic stretch were examined at 2, 6, 12, 24 h. Antibodies specific to p38MAPK phosphorylated forms and the total protein levels of the p38MAPK were examined using Western blot analysis. RESULTS: These results indicated that p38MAPK was activated during stretch-induced C2C12 cell differentiation. The level of phosphorylated protein was higher in the p38MAPK signaling pathway. The expression of total protein was maintained at baseline level. There were no significant differences between groups. Treatment of cells with specific p38MAPK inhibitor SB203580 could decrease the expression of myogenin, but not completely abolish the myogenin expression after stretch. CONCLUSION: p38MAPK signaling pathway plays an important role during stretch-induced differentiation process of C2C12 myoblasts, but is not activated exclusively in this process.