MiR-188-5p inhibits cell proliferation and migration in ovarian cancer via competing for CCND2 with ELAVL1.

MicroRNAs (miRNAs) were reportedly demonstrated to participate in ovarian cancer (OC) progression. Here, we inquired into the role of miR-188-5punderneath OC cell proliferation and migration. In this respect, our work examined the miR-188-5p expression and demonstrated its expression level in OC by qRT-PCR analysis. Enforced miR-188-5p expression resulted in a serious downfall of cell growth and mobility, and acceleration apoptosis in OC cells. Furthermore, we identified CCND2 as a target gene of miR-188-5p. RIP assay and luciferase reporter assay verified the interaction of miR-188-5p and CCND2 and exhibited that miR-188-5p greatly hindered the expression of CCND2. Besides, HuR stabilized CCND2 mRNA and counteracted the miR-188-5p suppressive effect on CCND2 mRNA. Functionally, rescue experiments also showed that miR-188-5p-mediated suppression on OC cell proliferation and migration was reverted by CCND2 or HuR overexpression. Our study found miR-188-5p was a tumor suppressor in OC via competing for CCND2 with ELAVL1, contributing to coming up with novel clues for OC therapies.

LncRNA SNHG8 accelerates proliferation and inhibits apoptosis in HPV-induced cervical cancer through recruiting EZH2 to epigenetically silence RECK expression.

Infection of human papillomaviruses (HPVs), such as subtypes HPV16 and HPV18 is carcinogenic to human and is prominent cause of HPV-positive cervical carcinoma (CC). A closer investigation into the mechanism of HPV-induced CC may stimulate the generation of an improved therapy treating cervical cancer. Our study herein interrogated the function of a small nucleolar RNA host gene 8 (SNHG8) in HPV-induced CC. As a result, a notable increase of SNHG8 in HPV-induced CC cells was found compared with HPV-negative CC cells. Functionally, it identified that SNHG8 aggravated the cell proliferation and migration in Cell Counting Kit-8 and transwell assays. Besides, flow cytometry apoptosis assay displayed that blockade of SNHG8 exacerbated apoptosis of HPV-positive CC cells. As detected by fluorescence in situ hybridization analysis and subcellular fractionation assay, SNHG8 was primarily expressed in the nucleus and exerted suppressive role on reversion inducing cysteine-rich protein with kazal motifs (RECK) expression, which implied a potential transcriptional regulation of SNHG8 on RECK level. Mechanically, SNHG8 was disclosed to interact with enhancer of zeste homolog 2 (EZH2) based on RNA immunoprecipitation assay. ChIP assay further unveiled the occupancy of EZH2 in the promoter region of RECK. An additional chromatin immunoprecipitation assay highlighted that SNHG8 intensified the enrichment of EZH2 and H3K27me3 in RECK promoter region. Altogether, it reflected that SNHG8 recruited EZH2 to downregulate RECK expression, leading to HPV-induced CC aggravation.

Hepatic flare after telbivudine withdrawal and efficacy of postpartum antiviral therapy for pregnancies with chronic hepatitis B virus.

BACKGROUND AND AIM: The efficacy of telbivudine for breaking vertical transmission of hepatitis B virus has been well established. Data on the risk of postpartum flare after telbivudine withdrawal and efficacy of extended antiviral therapy after delivery are limited. METHODS: Chronic hepatitis B virus-infected women who received telbivudine beginning at week 24 or 28 of gestation were enrolled and then followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed. RESULTS: Of the 241 women who finished 52 weeks of follow-up, 33.6% had elevated serum alanine aminotransferase (ALT) during pregnancy. Telbivudine administration resulted in ALT normalization in 85.2% before delivery. Compared with women having a normal ALT level throughout pregnancy, those with elevated ALT had a significantly higher rate of ALT flare after telbivudine withdrawal (25.0% vs 11.9%; χ2 = 4.273, P = 0.039). Multivariate analysis indicated that only ALT elevation during pregnancy correlated with postpartum flare after telbivudine withdrawal. Those women with elevated ALT during pregnancy continued antiviral treatment to 52 weeks postpartum and had a significantly higher HBeAg seroconversion rate (P = 0.001) and a notable decrease in HBsAg titers (P = 0.001). CONCLUSION: It is safe for the majority of women to withdraw telbivudine after delivery, whereas exciting serological response encourages extended antiviral therapy for mother with ALT elevation during pregnancy.

[Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein titer in infants born to mothers with positivity for hepatitis B surface antigen].

OBJECTIVE: To conduct a prospective randomized controlled trial of infants born to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein (HBS) induced by treatment with combined immunoprophylaxis (200 IU hepatitis B immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group. METHODS: Two-hundred-and-sixty-nine infants born to HBsAg positive mothers were given combined immunoprophylaxis at birth, and the venous blood samples (at birth, and 1, 7 and 12 months) were tested for HBV DNA load, and HBsAg and anti-HBS titers. RESULTS: The overall 1-year protective rate of combined immunoprophylaxis was 95.9%. There was no significant difference between the infectious rates of infants given the 5 mug or the 10 mug hepatitis B vaccine (x2 = 0.876, P = 0.377). The geometric mean titers (GMTs) of anti-HBS were 144.1 mIU/ml at 1-month old and 564.9 mIU/ml at the age of 7 months old (the highest point), but declined to 397.6 mIU/ml at the age of 12 months old. The rate of infants with anti-HBS titer less than 100 mIU/ml was 20.9%, and that of less than 10 mIU/ml was 7.4% at 7-month-old; the rate of infants with anti-HBS titer less than 100 mIU/ml increased to 30.2% and that of less than 10 mIU/ml increased to 15.9% at 12-month-old. At 7-month-old, the GMT of the 10 mug vaccine group was higher than that of the 5 mug vaccine group (675.3 mIU/ml vs. 25.0 mIU/ml, P = 0.001) and the rate of infants with anti-HBS titer less than 10 mIU/ml was significantly lower in the 10 mug vaccine group (2.3% vs. 12.6%, P = 0.002); at 12-month-old, the rate of infants with anti-HBS titer less than 100 mIU/ml was also significantly lower in the 10 mug group (20.6% vs. 40.2%, P = 0.001). CONCLUSION: Combined immunoprophylaxis is therapeutically efficacious for treating infants born to HBsAg positive mothers. Monitoring these infants' anti-HBs titer will help to identify non- or low-responders in a timely manner. The high-dose hepatitis B vaccine is preferable to the low-dose, and should be considered for use in immunization strategies for these infants.

No response to hepatitis B vaccine in infants born to HBsAg(+) mothers is associated to the transplacental transfer of HBsAg.

BACKGROUND: No or low hepatitis B (HB) vaccine response is more frequent in infants from HBsAg(+) mothers than those from HBsAg(-). Our previous study found temporary positivity of HBsAg in infants from HBsAg(+) mothers. In this study, we hypothesized that HBsAg in infant blunt immune response to standard hepatitis B vaccination. METHODS: A total of 328 consecutive HBsAg(+) mothers and their offspring were enrolled. Blood samples were taken from mothers and their infants and quantified for HBsAg, anti-HBs titer and HBV DNA load concentration; Placenta samples were collected to stain for HBsAg. RESULTS: First, 6.7% infants (22/328) showed anti-HBs titer lower than 10 mIU/mL after HB vaccination (non-response to HB vaccine). HBsAg(+) newborns showed higher risk of non-response than HBsAg(-) infants (13.0% versus 5.0%, p = 0.016). Infants from high HBsAg titer mothers displayed higher risk of HBsAg positivity at birth than those from low titer mothers (45.3% versus 2.8%, p < 0.001). HBsAg titer in mothers of HBsAg(+) newborns was much higher than mothers of HBsAg(-) newborns (p < 0.001). All those data supported HBsAg can be transferred through placenta. Our hypothesis was further reinforced by immunostaining with specific antibody against HBsAg, a substantial higher prevalence (87.5% versus 30.8%, p = 0.024) and stronger immunostaining (p = 0.008) was demonstrated in HBsAg(+) group comparing with placenta of the HBsAg(-) group. CONCLUSION: No response to HB vaccine in infants of HBsAg(+) mothers was associated to the transplacental transfer of HBsAg.