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Objective To investigate the effect and mechanism of silencing long non-coding RNA (lncRNA) LINC00472 on lipopolysaccharide (LPS)-induced renal tubular epithelial cell injury. Methods The human renal tubular epithelial cell line HK-2 (hereinafter referred to as HK-2 cells) was cultured in vitro and randomly divided into the control group, LPS group, LPS + si-LINC00472 group, LPS + si-NC group, LPS + miR-136-3p group, LPS + miR-NC group group, LPS + si-LINC00472 + anti-miR-136-3p group, and LPS + si-LINC00472 + anti-miR-NC group. Cells in the LPS + si-LINC00472 group were transfected with si-LINC00472, LPS + si-NC group with si-NC, LPS + miR-136-3p group with miR-136-3p, LPS + miR-NC group with miR-NC, LPS + si-LINC00472 + anti-miR- 136-3p group with si-LINC00472 + anti-miR-136-3p, and LPS + si-LINC00472 + anti-miR-NC group with si-LINC00472 + anti-miR-NC, followed by 1 μg/mL LPS stimulation for 24 h after 6-hour transfection, respectively. The cells in the LPS group were not transfected and were only stimulated with 1 μg/mL LPS for 24 h. The cells in the control group were routinely cultured without transfection and LPS stimulation. After the intervention, the cells in each group were collected, and RT-qPCR was used to detect the expression of lncRNA LINC00472 and miR-136-3p. The levels of IL-6 and IL-8 in the culture supernatant were detected by ELISA, and the binding sites of lncRNA LINC00472 and miR-136-3p, miR-136-3p and PDCD4 were predicted by Lnc-Base Predicted v.2 online prediction website and starBase database. The targeted regulatory relationship between lncRNA LINC00472 and miR-136-3p, miR-136-3p and PDCD4 was verified by dual-luciferase reporter gene experiments, and the protein expression of PDCD4 was detected by Western blotting. Results The relative expression of lncRNA LINC00472 in the LPS group was significantly higher than that in the control group, the relative expression of miR-136-3p was significantly lower than that in the control group, the cell viability was also significantly lower than that in the control group, and the levels of IL-6 and IL-8 in the culture supernatant were significantly higher than those of the control group (all P< 0. 05). The relative expression of lncRNA LINC00472 in the LPS + si-LINC00472 group was significantly lower than that in the LPS + si-NC group, the relative expression of miR-136-3p was significantly higher than that in the LPS + si-NC group, the cell activity was also significantly higher than that in the LPS + si-NC group, and the levels of IL-6 and IL-8 in the culture supernatant were significantly lower than those in the control group (all P<0. 05). The relative expression level of miR-136-3p and cell activity in LPS + miR-136-3p group were significantly higher than those in the LPS + miR-NC group, while the apoptosis rate, the levels of IL-6 and IL-8 in the culture supernatant and the relative expression of PDCD4 protein were significantly lower than those in the LPS + miR-NC group (all P<0. 05). The relative expression level of miR- 136-3p and the cell activity in the LPS + si-LINC00472 + anti-miR-136-3p group were significantly lower than those in LPS + si-LINC00472 + anti-miR-NC group, but the levels of IL-6 and IL-8 in culture supernatant and the relative expression of PDCD4 protein were significantly higher than those in the LPS + si-LINC00472 + anti-miR-NC group (all P<0. 05). Predicted by LncBase Predicted v.2 online prediction website and starBase database and verified by dual luciferase reporter gene experiments, lncRNA LINC00472 had a binding site with miR-136-3p, and miR-136-3p had a binding site with PDCD4. Conclusion Silencing lncRNA LINC00472 could alleviate LPS-induced renal tubular epithelial cell injury by promoting the expression of miR-136-3p and inhibiting the expression of PDCD4. [ABSTRACT FROM AUTHOR]

Objective: Coronary artery disease (CAD) is a cardiovascular disease that poses a fatal threat to human health, and the identification of potential biomarkers may help to delineate its pathophysiological mechanisms. Accumulating evidence has implicated microRNAs (miRNAs) in the pathogenesis and development of cardiovascular diseases. The present study aims to identify the expression of miRNA-136-3p (miR-136-3p) in CAD and further investigate its functional relevance in myocardial injury both in vitro and in vivo. Methods: Initially, CAD models were induced in rats by high-fat diet and intraperitoneal injection of pituitrin. Next, the effect of overexpressed miR-136-3p on cardiac function and pathological damage in myocardial tissue, cardiomyocyte apoptosis, oxidative stress and inflammatory response were assessed in CAD rats. Rat cardiac microvascular endothelial cells (CMECs) were isolated and cultured by the tissue explant method, and the CMEC injury model was induced by homocysteine (HCY). The function of miR-136-3p in vitro was further evaluated. Results: miR-136-3p was poorly expressed in the myocardial tissue of CAD rats and CMEC injury models. In vivo assays indicated that overexpressed miR-136-3p could improve cardiac function and alleviate pathological damage in myocardial tissue, accompanied by reduced oxidative stress and inflammatory response. Moreover,in vitro assays suggested that overexpression of miR-136-3p enhanced proliferation and migration while inhibiting apoptosis of HCY-stressed CMECs. Notably, we revealed that EIF5A2 was a target gene of miR-136-3p, and miR-136-3p inhibited EIF5A2 expression and activation of the Rho A/ROCK signaling pathway. Conclusion: In conclusion, the overexpression of miR-136-3p could potentially impede myocardial injury in vitro and in vivo in CAD through the blockade of the Rho A/ROCK signaling pathway, highlighting a potential miR-136-3p functional relevance in the treatment of CAD.

Objective: Coronary artery disease (CAD) is a cardiovascular disease that poses a fatal threat to human health, and the identification of potential biomarkers may help to delineate its pathophysiological mechanisms. Accumulating evidence has implicated microRNAs (miRNAs) in the pathogenesis and development of cardiovascular diseases. The present study aims to identify the expression of miRNA-136-3p (miR-136-3p) in CAD and further investigate its functional relevance in myocardial injury both in vitro and in vivo. Methods: Initially, CAD models were induced in rats by high-fat diet and intraperitoneal injection of pituitrin. Next, the effect of overexpressed miR-136-3p on cardiac function and pathological damage in myocardial tissue, cardiomyocyte apoptosis, oxidative stress and inflammatory response were assessed in CAD rats. Rat cardiac microvascular endothelial cells (CMECs) were isolated and cultured by the tissue explant method, and the CMEC injury model was induced by homocysteine (HCY). The function of miR-136-3p in vitro was further evaluated. Results: miR-136-3p was poorly expressed in the myocardial tissue of CAD rats and CMEC injury models. In vivo assays indicated that overexpressed miR-136-3p could improve cardiac function and alleviate pathological damage in myocardial tissue, accompanied by reduced oxidative stress and inflammatory response. Moreover,in vitro assays suggested that overexpression of miR-136-3p enhanced proliferation and migration while inhibiting apoptosis of HCY-stressed CMECs. Notably, we revealed that EIF5A2 was a target gene of miR-136-3p, and miR-136-3p inhibited EIF5A2 expression and activation of the Rho A/ROCK signaling pathway. Conclusion: In conclusion, the overexpression of miR-136-3p could potentially impede myocardial injury in vitro and in vivo in CAD through the blockade of the Rho A/ROCK signaling pathway, highlighting a potential miR-136-3p functional relevance in the treatment of CAD. [ABSTRACT FROM AUTHOR]

Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Coupled angiogenesis and osteogenesis via distinct type‐H vessels orchestrates subtle biological processes of bone homeostasis. The dysfunction of angiogenesis and osteogenesis contributes to decreased bone mass during the development of osteopenia. Herein, we identified microRNA‐136‐3p was remarkedly downregulated in the mouse model of alcohol‐induced osteopenia. Following the alcohol administration, downregulated microRNA‐136‐3p significantly suppressed vascularization and osteogenic differentiation in human umbilical vein endothelial cells (HUVECs) and bone mesenchymal stem cells (BMSCs), respectively. Furthermore, microRNA‐136‐3p could target phosphatase and tensin homolog deleted on chromosome ten (PTEN) in both HUVECs and BMSCs, thus substantially modulating the capacity of vessel formation and osteogenic differentiation. In the mouse model, microRNA‐136‐3p Agomir ameliorated alcohol‐induced osteopenia, with the concomitant restoration of bone mass and type‐H vessel formation. For the first time, this study demonstrated the pivotal role of microRNA‐136‐3p/PTEN axis in regulations of vascularization and bone formation, which might become the potential therapeutic target of alcohol‐induced bone loss. [ABSTRACT FROM AUTHOR]