SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A.

Silent information regulator 6 (SIRT6) is broadly considered as a tumor suppressor due to its function in the suppression of oncogene expression. However, the role of SIRT6 in colorectal cancer stem cells (CSCs) remains uncharacterized. In the present study, it was demonstrated that SIRT6 expression was reduced in colorectal CSCs. Overexpression of SIRT6 in colorectal CSCs did not induce cell apoptosis. However, SIRT6 significantly inhibited cell proliferation, colony formation and induced G0/G1 phase arrest in colorectal CSCs. In addition, SIRT6 repressed the expression of cell division cycle 25A (CDC25A), an oncogenic phosphatase. Chromatin immunoprecipitation experiments indicated that SIRT6 directly bound to the CDC25A promoter and decreased the acetylation level of histone H3 lysine 9. Altogether, these data indicated that SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A.

Bile acid levels and risk of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy: A meta-analysis.

AIM: We aimed to determine the association between maternal total bile acid (TBA) levels and the risks of adverse perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP) based on a meta-analysis study. METHODS: We searched PubMed for articles published from 2000 to 2015 with a focus on ICP and restriction to the English language. The main perinatal outcomes were preterm birth (PTB), meconium-stained amniotic fluid (MSAF), asphyxia, or respiratory distress syndrome (RDS). Relative risk (RR) with 95% confidence intervals (CI) was the summary statistic. We used a random- or fixed-effects model to calculate the pooled RR according to the heterogeneity test. Subgroup analyses were performed by region and study design. RESULTS: Nine eligible related citations fulfilled the inclusion criteria and were included in this study. Compared with pregnant women with a serum TBA < 40 µmol/L, severe ICP (TBA ≥ 40 µmol/L) was associated with a significantly increased risk of adverse fetal outcomes (pooled RR, 1.96; 95%CI, 1.63-2.35), PTB (pooled RR, 2.23; 95%CI, 1.51-3.29), MSAF (pooled RR, 2.27; 95%CI, 1.81-2.85), and asphyxia or RDS (pooled RR, 1.67; 95%CI, 1.18-2.36). Sensitivity analysis suggested that the study design difference may be a major source of heterogeneity. No publication bias was demonstrated by Begg's test (P > 0.05). CONCLUSION: This meta-analysis indicates that maternal elevated bile acid levels are significantly associated with increased risks of overall adverse perinatal outcomes, PTB, MSAF, and asphyxia or RDS. Serum TBA levels seem to be a useful predictor for the risk of adverse perinatal outcomes.

Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development.

Preeclampsia (PE) is a major contributor to maternal morbidity and mortality. However, the molecular mechanisms underlying PE progression are not well characterized. Here, we investigated the role of miR-218 in PE development. The expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in preeclamptic placentae compared to normal placentae. miR-218 expression was induced by hypoxia and decreased after knockdown of HIF-1α in an extravillous trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed direct binding of HIF-1α to the promoters of SLIT2 and SLIT3. Bioinformatics analysis identified LASP1 as a direct target of miR-218. Overexpression of miR-218 repressed the expression of LASP1 at both the mRNA and protein level. Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the 3'-untranslated region of the LASP1 gene. Furthermore, expression of LASP1 rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together, these results indicated that miR-218 contributes to PE by targeting LASP1 to inhibit trophoblast invasion.

MicroRNA-409-3p inhibits osteosarcoma cell migration and invasion by targeting catenin-δ1.

Osteosarcoma is the most common primary bone cancer which is associated with early metastatic potential and poor prognosis. However, the molecular mechanisms underlying osteosarcoma progression are not well characterized. Here, we investigated the role of miR-409-3p in osteosarcoma metastasis. Osteosarcoma tissue showed decreased expression of miR-409-3p compared to adjacent non-tumorous tissue. The expression level of miR-409-3p was negatively correlated with osteosarcoma metastasis. Overexpression of miR-409-3p in osteosarcoma cells (U2OS) inhibited cell migration and invasion. Bioinformatics analysis showed that catenin-δ1 (CTNND1, p120-catenin) is a direct target of miR-409-3p. Overexpression of miR-409-3p repressed the expression of catenin-δ1 in U2OS cells at both mRNA and protein levels. Meanwhile, miR-409-3p repressed the activity of luciferase reporter containing the 3'-untranslated region (3'UTR) of CTNND1 gene. Furthermore, expression of catenin-δ1 rescued the inhibitory effect of miR-409-3p on cell migration and invasion. Altogether, these results indicated that miR-409-3p targets catenin-δ1 to repress osteosarcoma metastasis.

MicroRNA-218 targets adiponectin receptor 2 to regulate adiponectin signaling.

Adiponectin exerts an antidiabetic function through the adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). The mechanism regulating the expression of adiponectin receptors remains to be elucidated. Bioinformatics analysis demonstrated that microRNA (miR)­218 targets the 3' untranslated region (3'UTR) of the AdipoR2 mRNA. The present study aimed to investigate whether miR-218 regulated the expression of AdipoR2 using immunoblotting, reverse transcription quantitative polymerase chain reaction and luciferase assays. The protein level and the mRNA level of AdipoR2 were reduced when miR­218 was expressed in HepG2 cells. Additionally, overexpression of miR­218 repressed the activity of a luciferase reporter containing the 3'UTR of AdipoR2. Furthermore, the present study aimed to determine whether miR-218 regulated glucose metabolism through detecting signaling pathways and glucose uptake. The phosphorylation of AMP­activated protein kinase and p38 mitogen­activated protein kinase was reduced in miR­218­expressing cells. In addition, miR­218 inhibited adiponectin­induced glucose uptake. The present results suggested that miR­218 targets AdipoR2 to inhibit adiponectin signaling.

Expression of PI3-K, PKB and GSK-3 ß in the skeletal muscle tissue of gestational diabetes mellitus.

OBJECTIVE: To analyze the expression of phosphatidylinositol 3 kinase (PI3-K), protein kinase B (PKB) and glycogen synthase kinase 3 beta (GSK-3 ß) in skeletal muscle tissue of gestational diabetes mellitus (GDM). METHODS: A total of 90 cases of pregnant women were divided into observation group and control group according to the occurrence of GDM with 45 cases in either, and the expression of PI3-K, PKB, GSK-3 ß mRNA expression in skeletal muscle tissue was compared between two groups. RESULTS: The total PI3-K p85 protein was significantly higher in the observation group compared with the control group, the activity of PI3-K was lower than that of the latter; The total PKB, GSK-3 ß protein in skeletal tissue had no significant difference between two groups, while the serine phosphorylation levels of PKB and GSK-3ß were significantly lower in observation group compared with the control group. CONCLUSIONS: The downregulation of PI3-K, PKB and GSK-3ßin skeletal tissue of GDM caused by phosphorylation dysfunction of signaling molecules is the reason for insulin resistance and transporter function decline which lead to GDM.