Protein N‐arginine methyltransferases (PRMTs) participate in a number of cellular processes, including cell growth, nuclear/cytoplasmic protein shuttling, differentiation, RNA splicing and post‐transcriptional regulation. PRMT2 (also known as HRMT1L1) is clearly involved in lung function, the inflammatory response, apoptosis promotion, Wnt signaling and leptin signaling regulation through different mechanisms. In this study, we report the molecular and cell biological characterization of three novel PRMT2 splice variants isolated from breast cancer cells and referred to as PRMT2α, PRMT2β and PRMT2γ. Compared with the wild‐type PRMT2, these variants lack different motifs and therefore generate distinct C‐terminal domains. Confocal microscopy scanning revealed a distinct intracellular localization of PRMT2 variants, suggesting that the alternatively spliced C‐terminus of PRMT2 can directly influence its subcellular localization. Our findings reveal that these variants are capable of binding to estrogen receptor alpha (ERα) both in vitro and in vivo, and the N‐terminal regions of these variants contribute to ERα–PRMT2 interactions. Furthermore, these variants were proved to be able to enhance ERα‐mediated transactivation activity. Luciferase reporter assays showed that PRMT2s could modulate promoter activities of the ERα‐targeted genes of Snail and E‐cadherin. In addition, PRMT2 silencing could enhance 17β‐estradiol‐induced proliferation by regulating E2F1 expression and E2F1‐responsive genes in ERα‐positive breast cancer cells. Real‐time PCR and immunohistochemistry showed that overall PRMT2 expression was upregulated in breast cancer tissues and significantly associated with ERα positivity status both in breast cancer cell lines and breast cancer tissues. We speculate that PRMT2 and its splice variants may directly modulate ERα signaling and play a role in the progression of breast cancer.Structured digital abstract PRMT2 and AR colocalize by fluorescence microscopy (View interaction) PRMT2 physically interacts with AR by anti tag coimmunoprecipitation (View interaction) PRMT2 physically interacts with ER‐alpha by anti tag coimmunoprecipitation (View interaction) PRMT2 binds to ER‐alpha by pull down (View interaction) PRMT2 physically interacts with ER‐alpha by pull down (View interaction) ER‐alpha and PRMT2 colocalize by fluorescence microscopy (View interaction)

Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification. Additionally, gain- and loss-of-function studies of miR-32 confirmed promotion of VSMC calcification in mice through the enhanced expression of bonemorphogenetic protein-2, runt-related transcription factor-2(RUNX2), osteopontin, and the bone-specific phosphoprotein matrix GLA protein in vitro. Moreover, miR-32 modulated vascularcalcification progression by activating phosphoinositide 3-kinase (PI3K)signaling and increasing RUNX2 expression and phosphorylation by targeting the 3′-untranslated region of phosphatase and tensin homolog Mrna (PTEN) in mouse VSMCs. Furthermore, we detected higher miR-32 levels in plasmafrom patients with coronary artery disease with coronary artery calcification (CAC) as compared with levels observed in non-CAC patients (P = 0.016), further confirming miR-32 as a critical modulator and potential diagnostic marker for CAC.

Objective. Asprosin, a new adipocytokine, has reportedly been associated with glucose release, dyslipidemia, and insulin resistance (IR). However, the relationship of asprosin with metabolic syndrome (MetS) remains unknown. This study aimed to investigate serum asprosin levels in MetS as well as their association with various metabolic parameters in humans. Methods. A total of 131 consecutive patients with MetS, and 162 age-matched, healthy subjects were recruited for this study. Serum asprosin concentrations were determined using the enzyme-linked immunosorbent assay. Lipid profile, glucose, insulin, and inflammatory markers were also measured. Results. Serum asprosin levels were higher in subjects with MetS (23.52 [16.70, 32.05] ng/mL) than in controls (16.70 [12.87, 22.38] ng/mL; ), and they showed an increasing trend with increasing numbers of metabolic components ( for trend < 0.01). In all studied subjects, serum asprosin levels were positively correlated with body mass index, waist circumference, triglycerides, fasting plasma glucose, 2-hour plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) index, interleukin-6, and monocyte chemoattractant protein-1 and negatively correlated with high-density lipoprotein cholesterol ( ). In multiple linear regression, asprosin was independently and positively correlated with triglyceride and HOMA-IR ( ). Binary logistic regression revealed that asprosin was independently and positively correlated with the occurrence of MetS and IR, even after controlling for anthropometric variables, lipid profiles, and inflammatory markers. Conclusion. Asprosin is a potential metabolic-related adipokine and may be related to IR and MetS. This trial was registered with ChiCTR, ChiCTR1800018347.