MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures

Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA-DNA triplex formation. We have found that RNA-DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA-DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs

Low incidence of prostate cancer identified in the transition and anterior zones with transperineal biopsy

Teresa L Danforth,1 K Kent Chevli,1,2 Louis Baumann,1,2 Michael Duff1,21The State University of New York (SUNY), Buffalo, NY, 2Cancer Care of Western New York, Cheektowaga, NY, USAPurpose: Determine the incidence of anterior (AZ) and transition (TZ) zone prostate cancers using a transperineal mapping approach.Methods: A retrospective review of 137 patients with history of previous negative biopsy undergoing transperineal saturation biopsy for an elevated prostate-specific antigen (PSA), high-grade prostate intraepithelial neoplasia, atypical small acinar proliferation history, or abnormal digital rectal exam. The number of biopsy cores was determined by prostate volume and obtained using a predefined template. The electronic medical records were reviewed for patients' clinical and pathological characteristics.Results: Forty-one of 137 patients (31.4%) had positive biopsy for prostate adenocarcinoma; 11 were from 24-core, 19 from 36-core, and 11 from 48-core sampling. Glands > 45 mL had a mean of 1.7 previous biopsies and a PSA of 9.1 ng/mL. Glands < 30 mL were 1.3 and 6.3 ng/mL and glands 30–45 mL were 1.4 and 6.5 ng/mL. Glands < 45 mL had a higher number of positive biopsies per total cores. Seven patients chose active surveillance while 34 chose treatment. Of the 36- and 48-cores biopsies, 2.2% and 1.5%, respectively, were positive in the TZ. One patient was AZ-positive, 1 was TZ-positive, and 18 were peripheral zone (PZ)-positive alone. Twelve patients had cancer detected in PZ and TZ. Two patients developed urinary retention and one had a urine infection.Conclusion: Transperineal saturation biopsy is a safe and efficacious method of prostate cancer detection in patients with previous negative biopsy and high suspicion for cancer. Few cancers were found to originate in the TZ or AZ alone. We recommend that initial biopsy templates should sample PZ with less focus on the TZ.Keywords: carcinoma, prostate, biopsy, transperinea

Alcohol consumption and subclinical atherosclerosis among South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study

BackgroundSouth Asians are the second fastest growing ethnic group in the United States, and they have a high risk for cardiovascular disease (CVD). Moderate alcohol consumption has been associated with lower CVD risk in some race/ethnic groups, but the association of alcohol consumption and atherosclerosis in South Asians has not been investigated.Methods and resultsWe used data from 906 South Asian participants who participated in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort (2010-2012). Alcohol consumption was ascertained via questionnaire, coronary artery calcium (CAC) was measured with computed tomography, and common carotid artery intima-media thickness (cIMT) was measured using B-mode ultrasonography. We used multivariable regression models to examine cross-sectional associations of alcohol consumption with the presence and amount of CAC and cIMT. Compared with never drinkers, participants consuming 4-7 drinks/week had a 63% decreased odds of any CAC after adjusting for potential confounders and mediators. Participants consuming 4-7 drinks/week had significantly lower odds of CAC score between 1 and 300 [OR (95% CI): 0.34 (0.16-0.72)]. A similar inverse association was seen for the odds of CAC>300 [OR (95% CI): 0.28 (0.07-0.97)]. Alcohol consumption of >7 drinks/week was associated with a 0.096 mm increase in common-cIMT.ConclusionThere was an inverse association between the amount of alcohol intake and CAC among South Asians while a positive association was found between alcohol consumption and common-cIMT. Long-term follow-up of the MASALA cohort will examine prospective associations of alcohol intake with the progression of subclinical atherosclerosis, incident CVD events, and mortality

Association of Alcohol Consumption and Ideal Cardiovascular Health among South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162772/2/acer14422_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162772/1/acer14422.pd