Our present study revealed the inhibitory functions of miR-145 on angiogenesis through directly targeting on VEGF-A and ANGPT2 for the first time and proved the protective role of lncRNA-MALAT1 for BMECs under OGD condition through the direct regulation of miR-145.

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IntroductionLong non-coding RNAs (lncRNAs) were identified as an important regulator involved in the pathogenesis of osteoarthritis (OA). We aimed to evaluate whether lncRNA GACAT3 regulate OA progression by miR-195/TGF-β/Smad5 axis.Material and methodsExpression levels in tissue or chondrocytes were detected by RT-qPCR and Western blot. Effects of GACAT3 on cell viability, proliferation, apoptosis were evaluated. Targeted interactions of GACAT3, miR-195 and Smad5 were confirmed by dual luciferase reporter gene assay and biotin-coupled miRNA capture assay. Transfected or non-transfected cells were treated with TGF-β1 to verify role of TGF-β in mechanisms of OA progression.ResultsGACAT3 was overexpressed in OA tissues and associated with OA severity. After GACAT3 overexpression, the ability of cell viability and proliferation as well as proliferation-related genes was inhibited with enhanced level of apoptosis-related genes and Smad5. miR-195-5p was negatively targeted by GACAT3 and reversed effects caused by GACAT3. miR-195-5p negatively targeted Smad5. In the presence of TGF-β1, miR-195-5p mimics inhibited activation of Smad1/5, Smad5 and Smad2 compared with negative control. Immunofluorescence showed that miR-195-5p inhibited Smad1/5 activation and transfer to nucleus. In the presence of TGF-β1, GACAT3 facilitated the activation of TGF-β signaling. In clinical sample analysis, GACAT3 was positively correlated with Smad5 expression in OA patients.ConclusionsWe confirmed the up-regulation of GACAT3 in OA patients, and found that GACAT3 regulated the chondrocytes phenotypes by miR-195/TGF-β/Smad5 axis and in turn contributed to OA progression. Findings indicated that GACAT3 may act as a novel therapeutic target for controlling OA progression.