and never-married people (OR 1.32) had a higher risk for depression. Among elderly unmarried people, widowed people had a higher risk for depression than those who never married (OR 1.51). In conclusion, being unmarried was an important risk factor for depression in elderly people.

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Aberration in microRNA expression or DNA methylation is a causal factor for polycystic ovarian syndrome. However, the epigenetic interactions between miRNA and DNA methylation remain unexplored in PCOS. We conducted a novel integrated analysis of RNA-seq, miRNA-seq, and methylated DNA-binding domain sequencing on ovarian granulosa cells to reveal the epigenetic interactions involved in the pathogenesis of PCOS. We identified 830 genes and 30 miRNAs that were expressed differently in PCOS, and seven miRNAs negatively regulated target mRNA expression. 130 miRNAs' promoters were significantly differently methylated, while 13 were associated with miRNA expression. Furthermore, the hypermethylation of miR-429, miR-141-3p, and miR-126-3p′ promoter was found related to miRNA expression suppression and therefore their corresponding genes upregulation, including XIAP, BRD3, MAPK14, and SLC7A5. Our findings provide a novel insight in PCOS. The consequential reversal of genes silencing may participate in PCOS pathogenesis and served as potential molecular targets for PCOS.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. microRNAs (miRNAs) repress gene expression by binding to complementary sequences in the 3' untranslated region (3'UTR) of target mRNAs. Alternative polyadenylation (APA) are relevant to the variability of the 3'UTR of mRNA. However, the posttranscriptional dysregulation of miRNAs and APA in CRC are poorly understood.Method: In this study, we conducted small RNA sequencing to identify differentially expressed miRNAs (DERs) and their target genes. Function analysis on DER-target genes can explain the regulation roles of miRNAs in CRC. The mutual regulation of miRNAs and APA was analyzed by combining miRNA data to 3'UTR alteration using 3' termini of polyadenylated RNAs sequencing (3T-seq) technique, and this was validated using TCGA gene expression data.Results: Our results showed 64 significant differentially expressed miRNAs (DERs) in CRC patients. Their target genes were related to cell adhesion and transcription regulation and were prevailingly involved in the CRC-related pathway. Integrative analysis of the miRNA and APA profile revealed 16 DERs were correlated with 12 polyadenylation factors, and six of them were significantly differently expressed in CRC. We also found four DERs that lost binding sites due to APA and showed a positive correlation between the miRNA and gene expression.Conclusion: Our study found that miRNAs regulated APA by modulating key polyadenylation factors, and several miRNAs lost their suppression on mRNA due to APA. Associating this with gene expression may provide some important clues for a deeper study of posttranscriptional cellular regulation and biomarker research in CRC. Our data provided the first evidence that the interaction between miRNAs and APA associated with gene expression could serve as biomarkers for CRC, suggesting that hsa-miR-133a-Frontiers in Genetics | www.frontiersin.org 3p and MLEC, hsa-miR-145-5p and SET, hsa-miR-1-3p and PPIA, and hsa-miR-378d and YY1 might be novel and potential biomarkers in improving the diagnosis of CRC.

Aims:We prospectively examined the relationship between metabolic syndrome (MetS) and incident chronic kidney disease (CKD) among middle-aged and elderly Chinese, and conducted a systematic review and meta-analysis of all cohort studies on this topic. Materials and Methods:Our research data were derived from the China Health and Retirement Longitudinal Study. Participants (n=5752, age ≥45 years) without CKD (defined as estimated glomerular filtration rate <60 ml/min/1.73m 2 ) at baseline were followed up for 4 years. We applied logistic regressions to examine the association of MetS with incident CKD. In addition, we pooled our effect estimates and those from previous cohort studies in the meta-analysis. Results:In a 4-years follow-up, 61 (4.27%) developed CKD in participants with MetS versus 102 (2.36%) in participants without MetS. After adjustment for potential confounders, odds ratio for incident CKD was 1.82 [95% confidence interval (95% CI): 1.19-2.78] comparing participants with MetS with those without MetS.There was a linear positive association between the number of MetS components and incident CKD (p for trend <0.001). In the updated meta-analysis of 25 studies among 350,655 participants with 29,368 incident cases of CKD, the pooled relative risk of developing CKD in participants with MetS was 1.34 (95% CI: 1.28-1.39), compared with those without MetS.Conclusions: Individuals with MetS had higher risk of incident CKD in middle-aged and elderly Chinese adults, which was supported by a comprehensive review of cohort studies from multiple populations. It may be advisable to routinely monitor renal functions among individuals with MetS.