An increasing number of studies have suggested that microRNAs (miRNAs) are involved in the progress of many human cancers including osteosarcoma (OS). Especially, microRNA-18a-5p (miR-18a-5p) has been reported to associate with the occurrence, development and clinical outcomes of human cancers. Therefore, we investigated the functions of miR-18a-5p in OS. Reverse transcription-quantitative PCR (RT-qPCR) showed that miR-18a-5p was significantly upregulated in OS tissues and cell lines (MG-63 and Saos-2). The overexpression of miR-18a-5p was found to significantly promote cell migration and invasion in MG-63 cells via Transwell assay. Moreover, luciferase reporter assays indicated that interferon regulatory factor (IRF)2 was a direct target of miR-18a-5p. IRF2 was downregulated in MG-63 and Saos-2 cell lines. Furthermore, Transwell analysis showed that the knockout of IRF2 promoted cell migration and invasion in MG-63 cells. Carcinogenesis of miR-18a-5p was reversed by the overexpression of IRF2 in OS. In conclusion, miR-18a-5p promoted the invasion and migration of OS cells through inhibiting IRF2 expression. Thus, miR-18a-5p might act as a potential target for the diagnosis and treatment of OS in the future.
Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in the elderly. This study focused on apoptosis and explored the modulating effects of long non‐coding (lncRNAs) prostate androgen‐regulated transcript‐1 (PART‐1) on chondrocytes apoptosis. In the present study, the PART‐1 expression level was down‐regulated in the OA cartilages. Silence of PART‐1 decreased the cell viability and promoted chondrocytes apoptosis. Overexpression of PART‐1 could reverse the effects induced by interleukin 1β (IL‐1β) stimulation, thus slowing down the apoptosis rate. MiR‐590‐3p was found to be the potential target, and RNA immunoprecipitation and luciferase activity assay confirmed the binding between PART‐1 and miR‐590‐3p. Moreover, miR‐590‐3p was down‐regulated by PART‐1 and was negatively associated with PART‐1. Transforming growth factor‐beta receptor type 2 (TGFBR2) was positively associated with PART‐1. Down‐regulation of PART‐1 decreased cell viability and induced cell apoptosis, which was partially reversed by miR‐590‐3p silence or TGFBR2 overexpression; while overexpression of PART‐1 increased the cell viability and decreased the caspase 3 activity and apoptotic rates, and the effects were partially attenuated by miR‐590‐3p overexpression or silence of TGFBR2 in IL‐1β‐stimulated chondrocytes. Knock‐down of PART‐1 down‐regulated both Smad3 and p‐Smad3 protein levels, which was reversed by miR‐590‐3p inhibition or TGFBR2 overexpression. Smad3 expression level was lower in the OA group than that in the normal group and was positively associated with the PART‐1 expression level. Collectively, the study revealed that lncRNA PART‐1 regulates the apoptosis of chondrocytes in OA by acting as a sponge for miR‐590‐3p, which subsequently regulates TGFBR2/Smad3 signalling.
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