Chikusetsu saponin Ⅳa ameliorates myocardial hypertrophy of rats through regulating expression of miR199a-5p/Atg5 / 中国中药杂志

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.

MiR-192/-215 Regulates the Biological Functions of Gastric Cancer Cells by Targeting BIVM / 中山大学学报(医学科学版)

[Objective] To investigate the molecular mechanism of miR-192/-215 targeting BIVM in human gastric cancer.[Methods] First,BIVM was the target gene of miR-192/-215 screened by the target gene prediction in solico and gene microarrays.Real-time quantitative PCR verified the results of the microarrays.Then the double-luciferase reporter plasmids were constructed to test that BIVM was the target gene of miR-192/-215.Subsequently,BIVM-siRNA was transfected,to know the effects of BIVM-siRNA on proliferation and apoptosis of gastric cancer cells.8 nude mice were randomly divided into two groups:BIVM-siRNA experimental group and NSC-siRNA control group.Gastric cancer cells transfected with BIVM-SiRNA were implanted under the skin of nude mice to observe the effect of BIVM on the tumorigenicity of gastric cancer cells.[Results] BIVM was screened as miR-192/-215 target gene by gene microarrays and quantitative PCR.Double-luciferase reporting assays were performed to identify the BIVM as miR-192/-215 target gene.The cell proliferation assays showed that BIVM promoted the proliferation of gastric cancer cells (P＜0.05).Test of flow cytometry showed that BIVM inhibited the apoptosis of gastric cancer cells (P＜0.05).Mouse tumorigenesis test confirmed that BIVM could promote gastric cancer cells growth in vivo (P＜0.05).[Conclusion] BIVM plays a role in the carcinogenesis of gastric cancer,and miR-192/-215 targeting BIVM promotes the development of gastric cancer.