miR-1307-3p overexpression inhibits cell proliferation and promotes cell apoptosis by targeting ISM1 in colon cancer.

BACKGROUND: colon adenocarcinoma (COAD) is the most common malignant tumor of gastrointestinal tract. Our study attempts to explore the effect of miR-1307-3p on biological function of COAD cells and its connection with isthmin 1 (ISM1). METHODS: The miRNA dataset and clinical information of patients with COAD were downloaded from The Cancer Genome Atlas (TCGA) database. The survival prognosis was analyzed by GGSURV package from R. MicroRNA (miR)-1307-3p was identified by identifying overlapping miRNAs that target ISM1, across two databases (miRDB and Targetscan). Dual luciferase reporter assay was employed to scrutinize the relationship between miR-1307-3p and ISM1. RT-PCR was used to quantify miR-1307-3p and ISM1 expression of colon cancer tissues and cell lines. Western blot was performed to quantify related protein expression. Flow Cytometry, CCK8 and colony formation assays were performed to evaluate the apoptosis, cell cycle, cell viability and proliferation of COAD cells. RESULTS: miR-1307-3p mRNA level decreased in both COAD tissues and cell lines. Overexpression of miR-1307-3p suppressed the proliferation, promoted apoptosis and arrested cell cycle at G1 phase, meanwhile, downregulation of ISM1 accelerated the proliferation, inhibited apoptosis and promote cell cycleprogression. The result of dual luciferase reporter assay indicated that miR-1307-3p targeted ISM1 directly and inhibited its expression. The functions of miR-1307-3p regulating cleaved caspase-3, cyclinD1, Ki67 protein levels and activation of Wnt3a/ß-catenin signaling pathway were reversed by ISM1. CONCLUSIONS: miR-1307-3p inhibited activation of Wnt3a/ß-catenin signaling through targeting downregulation of ISM1, thereby inhibited proliferation and promote apoptosis of COAD cells.

Associations between body composition profile and hypertension in different fatty liver phenotypes.

Background: It is currently unclear whether and how the association between body composition and hypertension varies based on the presence and severity of fatty liver disease (FLD). Methods: FLD was diagnosed using ultrasonography among 6,358 participants. The association between body composition and hypertension was analyzed separately in the whole population, as well as in subgroups of non-FLD, mild FLD, and moderate/severe FLD populations, respectively. The mediation effect of FLD in their association was explored. Results: Fat-related anthropometric measurements and lipid metabolism indicators were positively associated with hypertension in both the whole population and the non-FLD subgroup. The strength of this association was slightly reduced in the mild FLD subgroup. Notably, only waist-to-hip ratio and waist-to-height ratio showed significant associations with hypertension in the moderate/severe FLD subgroup. Furthermore, FLD accounted for 17.26% to 38.90% of the association between multiple body composition indicators and the risk of hypertension. Conclusions: The association between body composition and hypertension becomes gradually weaker as FLD becomes more severe. FLD plays a significant mediating role in their association.

MicroRNA­130a inhibits the proliferation, migration and invasive ability of hepatocellular carcinoma cells by downregulating Rho­kinase 2.

MicroRNA­130a (miR­130a) has been reported to be downregulated in hepatocellular carcinoma (HCC). However, the roles and underlying tumor­suppressive mechanisms of miR­130a in the pathogenesis of HCC remain unclear. In the current study, reduced expression of miR­130a was observed in tumor tissues of patients with HCC in addition to in four HCC cell lines, BEL­7402, MHCC97H, HepG2 and Huh7. Results of methyl thiazolyl tetrazolium (MTT) assays identified decreased growth rates of MHCC97H and HepG2 cells transfected with miR­130a mimics. The in vitro colony formation assays demonstrated that the number of colonies formed by cells transfected with miR­130a mimics and cells transfected with miR­130a inhibitors was lower and higher, respectively, than that formed by the cells transfected with miR­negative control. In addition, it was identified that overexpression of miR­130a reduced the migration and invasiveness of MHCC97H and HepG2 cells. Luciferase reporter assays demonstrated that miR­130a directly targeted the 3'­untranslated region of Rho­kinase 2 (ROCK2) mRNA. Northern and western blot analyses indicated that miR­130a could modulate the mRNA and protein expression of ROCK2. Additionally, small­interfering RNA­mediated knockdown of ROCK2 decreased the proliferation, migration and invasiveness of MHCC97H and HepG2 cells. Overall, these observation suggest that miR­130a is a regulator of ROCK2 and can inhibit proliferation, migration and invasive ability of HCC cells, at least in part, by suppressing the expression of ROCK2. The current study provides further insight into the molecular mechanisms of HCC pathogenesis and suggests a new potential biotarget for HCC treatment.