MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. While exosomal LINC00161 has been identified as a potential biomarker for HCC, its regulatory function and clinical values remain largely unknown. LINC00161 expressions in serum-derived exosomes from HCC patients and HCC cells were determined by qRT-PCR. The ability of proliferation, migration, and angiogenesis in HUVECs was assessed by MTT, Transwell, and tube formation. Luciferase reporter assay and AGO2-RIP assay were conducted to explore the interactions among LINC00161, miR-590-3p, and ROCK2. The level of ROCK signal-related proteins was examined by Western blotting and immunohistochemistry (IHC) assay. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of HCC cells. High levels of LINC00161 were detected in both serum-derived exosomes from HCC patients and the supernatants of HCC cell lines and were significantly associated with poor survival. Functional study demonstrated that exosomal LINC00161 derived from HCC-cells were significantly associated with enhanced proliferation, migration, and angiogenesis in HUVECs in vitro, all of which were effectively inhibited when LINC00161 was sliced with shRNA in HCC-cells. In vivo experiment showed that LINC00161 loss inhibited tumorigenesis and metastasis of HCC. Mechanistic study revealed that exosome-carried LINC00161 directly targeted miR-590-3p and induced its downstream target ROCK2, finally activating growth/metastasis-related signals in HCC. Exosome-carried LINC00161 promotes HCC tumorigenesis through inhibiting miR-590-3p to activate the ROCK2 signaling pathway, suggesting that LINC00161 may be used as potential targets to improve HCC treatment efficiency.

Exosomal LINC00161 promotes angiogenesis and metastasis via regulating miR-590-3p/ROCK axis in hepatocellular carcinoma

Purpose A series of microRNAs (miRNAs) have been identified as associated with the survival of patients with non-small-cell lung cancer (NSCLC). The aim of the present study was to explore whether combination of these experimentally validated individual miRNA biomarkers could be used to further increase their prognostic power in NSCLC. Patients and methods Based on previously validated NSCLC prognostic miRNAs, gene signatures that could discriminate high-risk subgroups with poor clinical outcome in four NSCLC miRNA expression datasets (GSE13937, GSE16025, The Cancer Genome Atlas Lung Adenocarcinoma, and TCGA lung squamous cell carcinoma) were developed using the SurvMicro tool. The potential of the miRNA signature established was validated by quantitative real-time PCR analysis of clinical NSCLC samples, and its prognostic power evaluated using the survivalROC method. Results We developed two miRNA signatures with prognostic significance for NSCLC, comprising 12- and 7-miRNAs. The 7-miRNA signature (miR-148b, miR-365, miR-32, miR-375, miR-21, miR-125b, and miR-155) was a subset of a 12-miRNA set that retained prognostic power across NSCLC cohorts. Compared with previously established miRNA signatures, our 7-miRNA signature has similar potential, while comprising fewer miRNA components. The prognostic ability of the 7-miRNA signature was validated experimentally in an independent NSCLC cohort using real-time PCR (HR=3.4847, 95% CI=1.3693-8.8680, P=0.0092), and this signature, combined with tumor pathological stage, had superior prognostic ability compared with tumor stage alone. Conclusion Our data indicate that the established 7-miRNA signature is simple, robust, and may have greater clinical prognostic utility for patients with NSCLC.

/pdf/establishment-and-validation-of-a-7-microrna-prognostic-557zgkejjx.pdf

Establishment and validation of a 7-microRNA prognostic signature for non-small cell lung cancer.

Background Recently studies uncovered associations between polymorphisms of interleukin genes and the risk of asthma. However, the relationship between polymorphisms of interleukin-7 gene and the risk of children asthma has not been discovered yet. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on interleukin-7 gene and the risk of children asthma. Methods We genotyped eight SNPs of interleukin-7 gene in blood samples from 437 asthma patients and 489 healthy controls to analyze potential associations of these SNPs with the risk of asthma in children. Results A missense SNP rs766736182 (odds ratio (OR) = 2.185, 95% confidence interval (CI) = 1.561-2.252, P-value = 8.69468E-19) of the interleukin-7 gene is associated with the risk of children asthma. Conclusions This study reveals that SNP rs766736182 of interleukin-7 is the risk factor for children asthma and implies potential role of immune system in the pathogenesis of children asthma.

Interleukin‐7 gene polymorphism rs766736182 associates with the risk of asthma in children

Background Recently, the rs5370 single nucleotide polymorphisms (SNPs) of Endothelin-1 (EDN1) showed association with the susceptibility of childhood primary nephrotic syndrome (CPNS). This study aims to investigate potential relationships between other EDN1 SNPs and CPNS. Methods Seven SNPs (rs5370, rs10478723, rs1476046, rs1800541, rs2070698, rs2071942, and rs9296344) of the EDN1 gene were genotyped in 579 CPNS patients and 586 age-matched healthy children. Then, we analyzed potential associations of the six SNPs with susceptibility of CPNS by using rs5370 as a conditional variant in a logistic regression model. SNP-SNP interaction analysis was performed to investigate the joint effects of the seven SNPs in the pathogenesis of CPNS. Results Independent with rs5370, only rs9296344 significantly associated (T vs C, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.57-0.88, P = .001) with the susceptibility of CPNS. Meanwhile, no joint effect among the analyzed seven SNPs was discovered in this study. Conclusions This study discovered that C allele of rs9296344 on EDN1 is a novel independent risk factor for CPNS.

Endothelin-1 rs9296344 associates with the susceptibility of childhood primary nephrotic syndrome.

// Bing He 1, * , Peng Lu 2, * , Lei Guan 1 , Ting Li 1 , Lei Zhang 1 , Qing-Ge Zhu 1 , Xiao-Xiao Ding 1 , Shi-Ming Zhang 1 , Xue-Mei Chen 1 , Jing Zhao 1 , Song Lin 1 , Zhi-Zhen Liu 1 , Fang-E Liu 3 , Wang Ma 4 and Hu-Qin Zhang 1 1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, P.R. China 2 Gastrointestinal Surgery Department, People’s Hospital of Zhengzhou, Zhengzhou 450052, P.R. China 3 Medical College, Xi’an Peihua University, Xi’an 710125, P.R. China 4 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China * These authors have contributed equally to this work Correspondence to: Bing He, email: hebinghb@mail.xjtu.edu.cn Fang-E Liu, email: liufange@fmmu.edu.cn Wang Ma, email: doctormawang@126.com Hu-Qin Zhang, email: huqzhang@mail.xjtu.edu.cn Keywords: omics; miRNA; HCC Received: June 13, 2017     Accepted: September 08, 2017     Published: October 17, 2017 ABSTRACT The miRNAs play important regulating roles in the pathogenesis of hepatocellular carcinoma (HCC). To uncover key regulating miRNAs in HCC that were neglected by traditional analyzing methods of transcriptomics data, we proposed a novel molecular-network-based omics’ (MNBO) method. With this method, we predicted HCC-regulating miRNAs, and confirmed the role of a novel miR-590-3P/ EED axis by a clinical study and in vitro , in vivo wet-experiments. The miR-590-3P is significantly down-regulated in HCC patients. And low level of miR-590-3P in HCC is associated with poor prognosis of patients. In HCC cell lines, the miR-590-3P suppressed cell proliferation by inhibiting the transformation G1 phase to S phases of the cell cycle. Moreover, the miR-590-3P inhibited migration and invasion of HCC cells. Further investigations indicated that miR-590-3P play its roles by inhibiting polycomb protein EED. The experiments in animal model implied miR-590-3P could be a potential therapeutic agent for HCC in the future. In conclusion, the discovery of miR-590-3P revealed the MNBO would be a useful strategy to uncover key regulating miRNAs in HCC.

Identifying key regulating miRNAs in hepatocellular carcinomas by an omics' method.

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Identifying key regulating miRNAs in hepatocellular carcinomas by an omics' method.