Objective MiR-499 has been reported to be expressed only in cardiomyocytes, and its expression would increase after acute myocardial infarction (AMI). miR-499 plays a role in the process of cardiomyocytes injury induced by hypoxia/reoxygenation (H/R), however, it still remains unclear. Results Hypoxia inhibited miR-499-5p expression and H/R induced apoptosis. SOX6 was a target gene of miR-499-5p, and high expression of miR-499-5p inhibited the expression of SOX6. MiR-499-5p reduced H9c2 cells injury by inhibiting the expression of SOX6, overexpression of which could reverse the effect of miR-499-5p on H9c2 cells. MiR-499-5p inhibited the levels of LDH and MDA, while overexpression of miR-499-5p inhibited H/R-induced cell apoptosis. MiR-499-5p could up-regulate the level of Bcl-2 and down-regulate the expression levels of Bax and caspase-3. However, SOX6 partially reversed these effects of miR-499-5p. Conclusion We proved that miR-499-5p inhibited H/R-induced cardiomyocytes injury by targeting SOX6. Our results suggested that miR-499-5p/SOX6 pathway may present a potential therapeutic target for the treatment of AMI.

Background: The Nuclear Dbf2-related (NDR1) kinase is a member of the NDR/LATS family, which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating Yes-associated protein (YAP) remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. This study aimed to investigate the role of NDR1-YAP pathway in GBM. Methods: Bioinformation analysis and immunohistochemistry (IHC) were performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing CCK-8, clone formation, immunofluorescence and flow cytometry, respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-immunoprecipitation and immunofluorescence to observe co-localization. Results: Bioinformation analysis and IHC of our patients’ tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to a lower survival rate. NDR1 could markedly reduce the proliferation and colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-overexpression group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phosphorylate YAP at S127 site. Meanwhile, NDR1 could mediate apoptosis process. Conclusion: In summary, our findings point out that NDR1 functions as a tumor suppressor in GBM. NDR1 is identified as a novel regulator of YAP, which gives us an in-depth comprehension of the Hippo signaling pathway.

Background: This study aimed to explore the effect of hyperglycemia-induced long noncoding RNA (lncRNA) metastasis-associated lung carcinoma transcript 1 (MALAT1) on microvascular endothelial cell activity. In addition, we investigated the possible downstream molecular regulatory mechanism in order to provide an adjunctive therapeutic target for the prognostic nerve recovery of cerebral small vessel disease (CSVD).Methods: A rat model of diabetes was induced by streptozotocin (STZ) injection in combination with a high-energy diet. The mixed model of CSVD and hyperglycemia was prepared by injection of homologous microemboli in vitro. Results of 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and enzyme-linked immunosorbent assay (ELISA) showed that the inhibition of lncRNA MALAT1 by siRNA in a high-glucose environment effectively alleviated the cell damage caused by high glucose (HG) and reduced the rate of apoptosis. We found that the upregulation of downstream miR-7641 and TPR (translocated promoter region) reduced the occurrence of cell damage and apoptosis. Results:The results of neurological deficit score showed that the scores of ICH group, HG group and HG + ICH group were significantly higher than those of Sham group, and the differences were statistically significant. The qPCR results showed that the MALAT1 level of the model group was significantly different from that of the sham group, and the expression levels of damage markers vWF and ICAM-1 were detected by Western blot (WB), which were significantly higher in the model group than in the sham group. The MTT cell activity assay showed that the addition of miR-7641 inhibitor or TPR short hairpin RNA (shRNA) into normally cultured cells reduced cell activity. ELISA results showed that low expression of miR-7641 increased the apoptosis rate of microvascular endothelial cells. Western blot (WB) results showed that the protein expression levels of BAX and cleaved caspase-3 (c-caspase-3) were negatively correlated with miR-7641. The regulation of TPR expression showed similar results.Conclusions: High blood glucose level induced the increase of lncRNA MALAT1 and regulated the expression of TPR by activating miR-7641 to promote the initiation of apoptosis of microvascular endothelial cells, aggravating the neurological dysfunction caused by CSVD.