Circulating miRNA-33: a potential biomarker in patients with coronary artery disease

Background: Circulating microRNAs (miRNA) are present in body fluids in stable, cell-free form. Likewise, these miRNAs can be identified in various stages of coronary artery disease (CAD) such as inflammation, endothelial dysfunction, proliferation and atherosclerosis among others. miRNA expression levels can be identified.

Aims and objectives: To determine the expression of circulating miRNAs (miR-126, miR-92, miR-33, miR-145 and miR-155) in CAD patients of Indian origin.

Material and methods: miRNA profiling analysis in blood plasma was performed by quantitative real-time-PCR (qRT-PCR) in 60 angiographically verified subjects including 30 CAD patients and 30 age- and gender-matched controls. Association between the expression of all five circulating miRNAs and clinical characteristics of patients with CAD were analysed using Medcalc statistics. The severity of CAD was assessed using SYNTAX score (SS).

Results: Expression of plasma miR-33 increased by 2.9 folds in CAD patients than in control group (p value ≥0.002) also it was found that miR-33 expression levels in mild cases (SS: ≤22) were significantly higher than CAD controls. There was a modest negative correlation between miR-33 and total cholesterol/high density lipoprotein ratio, triglycerides and very low density lipoprotein.

Conclusion: The study reports a significant association between increased levels of plasma miR-33 and CAD. Thus, plasma miR-33 appears to be a promising non-invasive biomarker, but requires further validation in a large cohort.     

Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels.

Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC.

Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan.

Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels.

Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.     

Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool

1. Download high-res image (242KB)
2. Download full-size image

     

Glycomics-driven discoveries in schistosome research

Schistosome glycans and glycoconjugates play a prominent role in the parasite's biology, in particular in the interaction with the human host. A large amount of structural data regarding glycosylation of different schistosome life stages and glycoconjugate subsets has been collected in the last decade, but many significant gaps in our knowledge of the schistosomal glycome remain. Here we will present a concise review of the already available data guided by a selection of recently generated stage-specific glycan profiles, and discuss implications and prospects of glycomics studies of schistosomes.     

circ_0001461靶向抑制miR-30a-5p对骨肉瘤细胞增殖和凋亡的影响

摘要 目的：探讨circ_0001461对骨肉瘤细胞增殖和凋亡的影响及调控机制。方法：采用实时荧光定量聚合酶反应（qRT-PCR）检测检测circ_0001461在骨肉瘤组织和细胞中的表达水平。在U2OS和HOS细胞中转染sh-NC和sh-circ_0001461后,采用CCK8检测细胞增殖情况,流式细胞术检测细胞凋亡情况,qRT-PCR检测增殖相关分子Ki-67 mRNA的表达水平,Western Blot检测凋亡相关分子Cleaved-caspase-3蛋白的表达水平。采用双荧光素酶报告基因检测circ_0001461和miR-30a-5p的结合情况。结果：circ_0001461在骨肉瘤组织中的表达水平明显高于癌旁正常组织（P<0.05）,circ_0001461在骨肉瘤细胞U2OS和HOS中的表达水平均明显高于成骨细胞NHOst（P<0.05）。低表达circ_0001461能够抑制骨肉瘤细胞U2OS和HOS的增殖和增殖相关分子Ki-67的表达（P<0.05）;促进骨肉瘤细胞U2OS和HOS的凋亡和凋亡相关分子Cleaved-caspase-3蛋白的表达（P<0.05）。双荧光素酶结果显示circ_0001461能够靶向结合miR-30a-5p。低表达circ_0001461能够促进miR-30a-5p的表达（P<0.05）,circ_0001461和miR-30a-5p在骨肉瘤组织中的表达呈负相关（P<0.05）。在U2OS细胞中共转染sh-circ_0001461和miR-30a-5p mimics后能够进一步加强单独转染sh-circ_0001461对U2OS细胞增殖和凋亡的影响（P<0.05）;在HOS细胞中共转染sh-circ_0001461和miR-30a-5p inhibitors后能够逆转单独转染sh-circ_0001461对U2OS细胞增殖和凋亡的影响（P>0.05）。结论：circ_0001461在骨肉瘤组织和细胞中明显高表达,低表达circ_0001461能够靶向促进miR-30a-5p的表达进而抑制骨肉瘤细胞增殖和促进细胞凋亡。     

血清miR-203、miR-217表达与急性髓系白血病患者预后的关系

摘要 目的：探究血清miR-203、miR-217表达与急性髓系白血病(AML)患者预后的关系。方法：选择2010年4月至2014年4月我院诊治的101例AML患者作为AML组,AML组根据治疗效果进一步分为完全缓解组和复发组,选择同期在我院体检的101例健康者作为健康组。采用荧光定量PCR检测各组的血清miR-203、miR-217表达水平,分析血清miR-203、miR-217表达水平与患者临床病理特征的关系,采用Kaplan-Meier法分析不同血清miR-203、miR-217表达水平AML患者的预后。结果：与健康组相比,AML组的血清miR-203、miR-217表达水平明显更低（P<0.05）。与完全缓解组相比,复发组的血清miR-203、miR-217表达水平明显更低（P<0.05）。血清miR-203表达水平与AML患者白细胞计数相关（P<0.05）,而血清miR-217表达水平与AML患者血小板计数相关（P<0.05）。血清miR-203相对高表达和miR-217相对高表达的AML患者5年生存率分别高于血清miR-203相对低表达和miR-217相对低表达患者（Log Rank ^miR-203 =17.870,Log Rank ^miR-217 =28.926,均P=0.000）。结论：血清miR-203、miR-217的表达水平与AML密切相关,检测血清miR-203、miR-217表达水平可能有助于评估AML患者的预后。     

The novel circ_0084904/miR-802/MAL2 axis promotes the development of cervical cancer

Circular RNAs (circRNAs) have been identified as critical regulators in human cancers, including cervical cancer (CC). However, the precise action of circ_0084904 in cervical carcinogenesis remains to be elucidated. The levels of circ_0084904, microRNA (miR)-802, and Mal, T cell differentiation protein 2 (MAL2) were checked by quantitative real-time PCR (qRT-PCR) or western blot. Ribonuclease R (RNase R) and subcellular localization assays were used to detect the stability and localization of circ_0084904, respectively. Cell colony formation ability was assessed by colony formation assay. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion abilities were gauged by transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to determine the direct relationship between miR-802 and circ_0084904 or MAL2. The xenograft experiments were performed to evaluate the role of circ_0084904 in tumor growth in vivo. Circ_0084904 was markedly up-regulated in CC tissues and cell lines. Silencing endogenous circ_0084904 impeded cell colony formation, cell cycle progression, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0084904 targeted miR-802, and the effects of circ_0084904 silencing were mediated by miR-802. MAL2 was directly targeted and inhibited by miR-802, and MAL2 was a functional target of miR-802. Moreover, circ_0084904 modulated MAL2 expression via miR-802. Our study identified circ_0084904 as a novel oncogenic driver in CC depending on the modulation of the miR-802/MAL2 axis, establishing the notion that silencing of circ_0084904 might represent a promising targeted therapy for CC.     

Overexpression of miR-493-3p suppresses ovarian cancer cell proliferation,migration and invasion through downregulating DPY30

Accumulating evidence has verified that the aberrant expression level of miR-493?3p is often associated with the occurrence of numerous cancers. Nevertheless, the expression level and effect of this microRNA in ovarian cancer (OC) remain largely unclear. Therefore, the molecular function of miR-493?3p in OC progression was systematically investigated in this study.The expression of miR-493?3p and DPY30 was assessed by qRT-PCR. The protein expression level of DPY30 in cell lines was further assessed by western blot. Cell viability was respectively examined in vitro functional experiments including CCK-8 assay, EdU assay, wound healing assay, colony formation and apoptosis assays as well as the scratch test and transwell assay. Bioinformatics analysis and luciferase reporter assays were performed to predict and clarity of the correlation between miR-493?3p and DPY30.The expression of miR-493?3p was significantly reduced in OC tissues and cells. Functional experimental results showed that miR-493?3p suppressed cellular proliferation, migration, invasion, but promoted apoptosis in OC cells. Mechanistically, we also confirmed that DPY30 could be directly targeted by miR-493?3p based on bioinformatics and dual-luciferase reporter analysis. Rescue experiments results indicated that the inhibitory effect of miR-493?3p on cellular proliferation, migration and invasion and the promotive effect of miR-493?3p on apoptosis was abolished by DPY30 overexpression.Our findings demonstrated the antitumor effect of miR-493?3p through targeting DPY30 in ovarian cancer, indicating that miR-493?3p might represent a promising target for ovarian cancer diagnosis and treatment.     

Long non-coding RNA small nucleolar RNA host gene 1 alleviates the progression of recurrent spontaneous abortion via the microRNA-183-5p/ZEB2 axis

Long non-coding RNAs (lncRNAs) have been elucidated to play vital roles in the phenotype of trophoblast cells. Nevertheless, the effect of SNHG1 has not been investigated on trophoblast cells in recurrent spontaneous abortion (RSA). We aim to investigate the effect of SNHG1 on the phenotype of trophoblast cells during RSA. The RSA mice were established by mating female CBA/J mice with male DBA/2 mice. Microarray analysis was applied in RSA mice, and SNHG1 was identified as a significantly downregulated lncRNA. SNHG1 improved pregnancy outcome and reduced embryo resorption in RSA mice. Trophoblast cell proliferation, apoptosis, migration, and invasion were investigated by CCK8, EdU, TUNEL, wound healing, and Transwell assays. SNHG1 promoted proliferation, migration, and invasion of trophoblast cells, and reduced apoptosis. Mechanistically, SNHG1 bound to miR-183-5p in trophoblast cells. Moreover, miR-183-5p directly targeted ZEB2. Rescue experiment showed that ZEB2 silencing reversed the ameliorative effect of SNHG1 on pregnancy outcome and the promotion of trophoblast activity in RSA mice by impaired the Wnt/β-catenin pathway. In conclusion, we found that SNHG1 plays a critical role in the progression of RSA via miR-183-5p/ZEB2 and Wnt/β-catenin signaling. It has potential to be a therapeutic marker of RSA.