Journal of biological regulators and homeostatic agents最新文献

Osteoporosis (OP) is among the most common frequent chronic metabolic bone diseases in postmenopausal women. Here, the effect and underlying mechanisms of miR-195-5p in OP were investigated both in vivo and in vitro. In this study, the microgravity (MG) environment was simulated in MC3T3-E1 cells, and miR-195-5p overexpression or SMURF1 knockdown model was constructed to test their effects on the proliferation, apoptosis and osteogenic differentiation of MC3T3-E1 cells. Furthermore, an OVX mouse model was constructed in vivo, and adenovirus-loaded miR-195-5p mimics were administered to the mice to overexpress miR-195-5p. HE staining and µCT were adopted to observe pathological changes of femur. The targeted relationship between miR-195-5p and SMURF1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment. The results indicated that miR-195-5p was down-regulated in the head of femur of OP mouse model and MC3T3-E1 cells subjected to MG microenvironment. In addition, overexpression of miR-195-5p promoted MC3T3-E1 cell osteogenic differentiation and inhibited apoptosis. Mechanistically, SMURF1 is identified as a target of miR-195-5p, and overexpressing miR-195-5p activates the BMP-2/SMAD/Akt/RUNX2 signal by inhibiting the SMURF1 expression. Moreover, SMURF1 downregulation accelerated the osteogenic differentiation of MC3T3-E1 cells and attenuated MG-mediated apoptosis. In addition, upregulating miR-195-5p reduced osteoporosis in the OVX mouse model, accompanied with SMURF1 downregulation and BMP-2/SMAD/Akt/RUNX2 pathway activation. Collectively, miR-195-5p enhances osteogenic differentiation of osteoclast and relieve OP progression in the mouse model through activation of the BMP-2/SMAD/Akt/RUNX2 axis by targeting SMURF1.

In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (Non-Small Cell Lung Cancer) cell lines H292 (denoted as H292S) and PC9 (denoted as PC9S) were used to establish gefitinibresistant NSCLC cell lines H292 and PC9 models. CCK-8 (Cell Counting Kit-8) method was used to test the drug resistance of the cells. circRNAs (circular RNAs) that were differentially expressed before and after resistance were screened by RNA sequencing technology. The effects of circSETD3 overexpression and interference on the sensitivity of gefitinib was observed to analyze the nuclear localization of circSETD3 and verify the interaction between circSETD3-miR-520h-ABCG2. The results showed that the most significant change in differential expression of human NSCLC cell lines before and after drug resistance was hsa_circ_0000567, that is, circSETD3, which is mainly present in the cytoplasm. In H292S and PC9S, compared with the negative control group, the cell proliferation ability of the overexpression group was significantly increased, and the apoptosis ability was significantly decreased. In H292R and PC9R, compared with the negative control group, the proliferation ability of the interference group was significantly decreased, and the apoptosis ability was significantly increased. Overexpression of circSETD3 to H292S and PC9S, the expression of ABCG2 increased significantly. Also, the expression of ABCG2 decreased significantly after transfection with miR-520h mimics. H292R and PC9R interfered with circSETD3, the expression of ABCG2 decreased significantly. Moreover, the expression of ABCG2 increased significantly after transfection with miR-520h inhibitor. In conclusion, circSETD3 can be used as a novel biomarker for lung cancer. It relieves miR-520h degradation of the transporter ABCG2 by down-regulating the miR-520h expression, causing gefitinib to be pumped out of the cell.