Dicer interacts with SIRT7 and regulates H3K18 deacetylation in response to DNA damaging agents.

Dicer participates in heterochromatin formation in fission yeast and plants. However, whether it has a similar role in mammals remains controversial. Here we showed that the human Dicer protein interacts with SIRT7, an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase, and holds a proportion of SIRT7 in the cytoplasm. Dicer knockdown led to an increase of chromatin-associated SIRT7 and simultaneously a decrease of cytoplasmic SIRT7, while its overexpression induced SIRT7 reduction in the chromatin-associated fraction and increment in the cytoplasm. Furthermore, DNA damaging agents promoted Dicer expression, leading to decreased level of chromatin-associated SIRT7 and increased level of H3K18Ac, which can be alleviated by Dicer knockdown. Taken together with that H3K18Ac was exclusively associated with the chromatin, our findings suggest that Dicer induction by DNA damaging treatments prevents H3K18Ac deacetylation, probably by trapping more SIRT7 in the cytoplasm.

Hepatitis B surface antigen inhibits MICA and MICB expression via induction of cellular miRNAs in hepatocellular carcinoma cells.

Hepatitis B surface antigen (HBsAg) seropositivity is an important risk factor for hepatocellular carcinoma (HCC), and HBsAg-transgenic mice have been reported to spontaneously develop HCC. The major histocompatibility complex class I-related molecules A and B (MICA and MICB) are NKG2D ligands that play important roles in tumor immune surveillance. In the present study, we found that HBsAg overexpression in HepG2 cells led to upregulation of 133 and downregulation of 9 microRNAs (miRNAs). Interestingly, several HBsAg-induced miRNAs repressed the expression of MICA and MICB via targeting their 3'-untranslated regions. In addition, the expression of MICA and MICB was significantly reduced upon HBsAg overexpression, which was partially restored by inhibiting the activities of HBsAg-induced miRNAs. Moreover, HBsAg-overexpressing HCC cells exhibited reduced sensitivity to natural killer cell-mediated cytolysis. Taken together, our data suggest that HBsAg supresses the expression of MICA and MICB via induction of cellular miRNAs, thereby preventing NKG2D-mediated elimination of HCC cells.

Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: a meta-analysis of diagnostic accuracy.

BACKGROUND AND AIM: Controlled attenuation parameter (CAP) is a novel ultrasound-based elastography method for detection of steatosis severity. This meta-analysis aimed to assess the performance of CAP. METHODS: PubMed, the Cochrane Library, and the Web of Knowledge were searched to find studies, published in English, relating to accuracy evaluations of CAP for detecting stage 1 (S1), stage 2 (S2), or stage 3 (S3) hepatic steatosis which was diagnosed by liver biopsy. Sensitivities, specificities, and hierarchical summary receiver operating characteristic (HSROC) curves were used to examine CAP performance. The clinical utility of CAP was also evaluated. RESULTS: Nine studies, with 11 cohorts were analyzed. The summary sensitivities and specificities values were 0.78 (95% confidence interval [CI], 0.69-0.84) and 0.79 (95% CI, 0.68-0.86) for ≥ S1, 0.85 (95% CI, 0.74-0.92) and 0.79 (95% CI, 0.71-0.85) for ≥ S2, and 0.83 (95% CI, 0.76-0.89) and 0.79 (95% CI, 0.68-0.87) for ≥ S3. The HSROCs were 0.85 (95% CI, 0.81-88) for ≥ S1, 0.88 (95% CI, 0.85-0.91) for ≥ S2, and 0.87 (95% CI, 0.84-0.90) for ≥ S3. Following a "positive" measurement (over the threshold value) for ≥ S1, ≥ S2, and ≥ S3, the corresponding post-test probabilities for the presence of steatosis (pretest probability was 50%) were 78%, 80% and 80%, respectively; if the values were below these thresholds ("negative" results), the post-test probabilities were 22%, 16%, and 17%, respectively. CONCLUSIONS: CAP has good sensitivity and specificity for detecting hepatic steatosis; however, based on a meta-analysis, CAP was limited in their accuracy of steatosis, which precluded widespread use in clinical practice.

Association between a lumican promoter polymorphism and high myopia in the Chinese population: a meta-analysis of case-control studies.

PURPOSE: To evaluate the relationship between lumican polymorphisms and high myopia in Chinese populations. METHODS: An electronic search was conducted in Pubmed, Embase, Cochrane Library and the China Biological Medicine Database for articles published prior to September 30, 2012. A meta-analysis was performed to assess heterogeneity, combine results and determine publication bias. RESULTS: This meta-analysis, including 1,545 subjects from 5 studies, indicated that Chinese lumican rs3759223 C allele carriers had a decreased risk of high myopia in comparison to T allele carriers (odds ratio: 0.531; 95% confidence interval, CI: 0.304-0.925; p = 0.025). There was some heterogeneity between studies. A metaregression showed that the mean axial length of controls weakens the effect of rs3759223 on high myopia (slope: -0.914; 95% CI: -1.490 to 0.337; p = 0.002). Sensitivity analysis confirmed the reliability and stability of this meta-analysis. CONCLUSION: Chinese lumican rs3759223 C allele carriers may be at reduced risk of high myopia.

Meta-analysis of the association between a polymorphism in microRNA-196a2 and susceptibility to colorectal cancer.

BACKGROUND/AIMS: To accurately evaluate the impact of the C/T polymorphism in microRNA (miRNA)-196a2 on the colorectal cancer (CRC) risk, by meta-analysis. METHODS: An electronic search for articles was conducted in PubMed, EMBASE, ISI Web of Science, and the Cochrane Library. The pooled odds ratio (OR) and its 95% confidence interval (CI) were used to assess the association through meta-analysis. RESULTS: 5 studies were used for analysis. The results showed a significant association between the miRNA-196a2 C/T polymorphism and CRC risk in the genetic models (C vs. T: OR = 1.168, 95% CI = 1.106-1.282, p = 0.001; CC vs. TT: OR = 1.368, 95% CI = 1.132-1.654, p = 0.001; TC/CC vs. TT: OR = 1.206, 95% = CI 1.035-1.405, p = 0.016; CC vs. TC/TT: OR = 1.254, 95% CI = 1.077-1.461, p = 0.004), with the exception of the TC-versus-TT model (TC vs. TT: OR = 1.130, 95% CI = 0.961-1.329, p = 0.138). In a subgroup analysis based on ethnicity, we identified a significant overrepresentation of the polymorphism in individuals of Asian ethnicity. CONCLUSION: This meta-analysis indicates a significant association between the miRNA-196a2 polymorphism and CRC risk.

Performance of shear wave elastography for differentiation of benign and malignant solid breast masses.

OBJECTIVES: To perform a meta-analysis assessing the ability of shear wave elastography (SWE) to identify malignant breast masses. METHODS: PubMed, the Cochrane Library, and the ISI Web of Knowledge were searched for studies evaluating the accuracy of SWE for identifying malignant breast masses. The diagnostic accuracy of SWE was evaluated according to sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC) curves. An analysis was also performed according to the SWE mode used: supersonic shear imaging (SSI) and the acoustic radiation force impulse (ARFI) technique. The clinical utility of SWE for identifying malignant breast masses was evaluated using analysis of Fagan plot. RESULTS: A total of 9 studies, including 1888 women and 2000 breast masses, were analyzed. Summary sensitivities and specificities were 0.91 (95% confidence interval [CI], 0.88-0.94) and 0.82 (95% CI, 0.75-0.87) by SSI and 0.89 (95% CI, 0.81-0.94) and 0.91 (95% CI, 0.84-0.95) by ARFI, respectively. The HSROCs for SSI and ARFI were 0.92 (95% CI, 0.90-0.94) and 0.96 (95% CI, 0.93-0.97), respectively. SSI and ARFI were both very informative, with probabilities of 83% and 91%, respectively, for correctly differentiating between benign and malignant breast masses following a "positive" measurement (over the threshold value) and probabilities of disease as low as 10% and 11%, respectively, following a "negative" measurement (below the threshold value) when the pre-test probability was 50%. CONCLUSIONS: SWE could be used as a good identification tool for the classification of breast masses.

Decreased dicer expression enhances SRP-mediated protein targeting.

We have shown that Dicer processes 7SL RNA into different fragments ranging from ∼20 to more than 200 nucleotides. Here we addressed the molecular functions of these 7SL RNA fragments and found that some of them functioned as dominant-negative regulators of the full-length 7SL RNA, interfering with signal recognition particle (SRP) complex formation. Transfection of these 7SL RNA fragments inhibited the expression of cell surface glycoproteins, the targeting of a reporter protein to the endoplasmic reticulum, and the secretion of secreted alkaline phosphatase. These results suggest that some Dicer-processed 7SL RNA fragments interfered with SRP-mediated protein targeting. Moreover, we showed that Dicer knockdown enhanced SRP-mediated protein targeting and that transfection of a mixture of the 7SL RNA fragments partially restored this effect. Our data indicate that Dicer can fine-tune the efficiency of SRP-mediated protein targeting via processing a proportion of 7SL RNA into fragments of different lengths.