海南人咀嚼槟榔引起的口腔鳞状细胞癌ceRNA网络分析

目的:构建咀嚼槟榔引起的口腔鳞状细胞癌（OSCC）的ceRNA网络,探究其表达异常可能影响的调节通路改变。方法:对咀嚼槟榔的OSCC及癌旁组织进行miRNA测序和lncRNA微阵列分析,并建立了ceRNA网络。结果:lncRNA-miRNA-mRNA网络由308个lncRNA,41个miRNA和115个mRNA组成。结论:GO和KEGG分析表明,ceRNA网络参与了MAPK、凋亡、p53和PI3K/Akt等不同的信号通路。     

Dysfunction of miR‐802 in tumors

Recent studies have shown that miR‐802 is abnormally expressed in many tumors. miR‐802 is expressed at low levels in tissues and cells of gastric cancer, colorectal cancer, breast cancer, cervical cancer, epithelial ovarian cancer, tongue squamous cell carcinoma, oral squamous cell carcinoma, esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma, and melanoma. In contrast, miR‐802 is overexpressed in hepatocellular carcinoma, bladder urothelial cancer, osteosarcoma, and cholesteatoma tissue cells. It should be noted that the results of studies on the expression of miR‐802 in pancreatic cancer, prostate cancer, and lung cancer are inconsistent. Current studies have found that miR‐802 can target and regulate genes in different tumors, and affect the regulation of the Wnt signaling pathway, EMT signaling pathway, PI3K/AKT signaling pathway, ERK signaling pathway, and Hedgehog signaling pathway. At the same time, miR‐802 is regulated by the endogenous competition of four ceRNAs, including circDONSON, IGFL2‐AS1, MIR155HG, and MIR4435‐2HG. This article reviews the abnormal expression of miR‐802 in a variety of tumors, expounds the mechanism by which miR‐802 affects tumor progression by regulating different target genes, and elaborates the network of miR‐802‐related ceRNAs. We also summarized the limitations of miR‐802 research and looked forward to the potential application of miR‐802 in the diagnosis and prognosis of tumors.     

CircRNA_0008194 functions as a ceRNA to promote invasion of hepatocellular carcinoma via inhibiting miR‐190a/AHNAK signaling pathway

BackgroundHepatitis B virus infection was identified as the main risk factor of hepatocellular carcinoma (HCC) in China, which induced a high morbidity and mortality. In recent years, circRNAs were reported involving in the oncogenesis and development of multiple malignant tumors.MethodBioinformatical analysis has been employed to predict the relevant circRNA with AHNAK. The loss of function and gain of function have been used by knocking‐down circRNA through the shRNA technology while overexpressing through lentivirus infection. Dual‐luciferase reporter assay was used to detect circRNA binding to miRNA and target genes. We further used immunoprecipitation technique to detect the binding ability between non‐coding RNAs.ResultsIn this study, according to the previous report, we mainly focused on AHNAK, which has been confirmed as an oncogene involving in the metastasis of HCC. Bioinformatics analysis showed that circ_0008194 could be spliced by AHNAK. In this study, the abnormal upregulated circ_0008194 in tumor tissues was detected. The positive correlation between circ_0008194 and AHNAK was also confirmed. Through knockdown and overexpression of circ_0008194, we conducted in vitro functional studies. We found circ_0008194 could induce the invasion of cells in vitro. Mechanically, circ_0008194 presented the binding ability with miR‐190a causing the suppression of miR‐190a expression, causing the competitive inhibition of AHNAK, resulting in the promotion of EMT.ConclusionOur results suggested that circ_0008194 may act as a sponge to adsorb miR‐190a, thereby promoting the expression of AHNAK and promoting the metastasis of liver cancer tumors.     

Circ_0001955 promotes non-small cell lung cancer cell proliferation and invasion by regulating MiR-29a-3p/NKIRAS2 axis to activate the nuclear factor-κB pathway

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Circular RNAs (circRNAs) have been widely reported to play a role in the pathogenesis of various tumors. Nevertheless, the function of circ_0001955 in NSCLC progression has not been explored yet. This study aims to explore the functions of circ_0001955 in NSCLC and investigate its regulatory molecular mechanism. First, we determined that circ_0001955 was upregulated in NSCLC cells. Subsequently, we demonstrated that knockdown of circ_0001955 restrained cell proliferation and invasion. In vivo experiments further proved the suppressive effect of circ_0001955 silence on tumor growth. Mechanism assays revealed that circ_0001955 enhanced nuclear factor-κB (NF-κB) inhibitor interacting Ras-like protein 2 (NKIRAS2) expression by sponging microRNA-29a-3p (miR-29a-3p). Upregulation of NKIRAS2 led to the deceased level of IκBβ but increased levels of nuclear p65, thus activating the NF-κB signaling pathway. In conclusion, Circ_0001955 activates the NF-κB pathway to promote NSCLC cell proliferation and invasion by regulating miR-29a-3p/NKIRAS2 axis.     

Identification of circular RNAs as novel biomarkers and potentially functional competing endogenous RNA network for myelodysplastic syndrome patients

Circular RNAs (circRNAs) have been identified to exert vital biological functions and can be used as new biomarkers in a number of tumors. However, little is known about the functions of circRNAs in myelodysplastic syndrome (MDS). Here, we aimed to investigate circRNA expression profiles and to investigate the functional and clinical value of circRNAs in MDS. Differential expression of circRNAs between MDS and control subjects was analyzed using circRNA arrays, in which we identified 145 upregulated circRNAs and 224 downregulated circRNAs. Validated by real-time quantitative PCR between 100 MDS patients and 20 controls, three upregulated (hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_104634) and three downregulated (hsa_circRNA_103846, hsa_circRNA_102817, and hsa_circRNA_102526) circRNAs matched the arrays. The receiver operating characteristic curve analysis of these circRNAs showed that the area under the curve was 0.7266, 0.8676, 0.7349, 0.7091, 0.8806, and 0.7472, respectively. Kaplan-Meier survival analysis showed that only hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817 were significantly associated with overall survival. Furthermore, we generated a competing endogenous RNA network focused on hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that the three circRNAs were linked with some important cancer-related functions and pathways.     

Integrating analysis of circular RNA and mRNA expression profiles in doxorubicin induced cardiotoxicity mice

Doxorubicin (DOX)-induced cardiotoxicity impedes its clinical application, but the mechanisms have not been thoroughly elucidated. Based on circRNA and mRNA expression profiles, we illustrated RNA expression signature changes during DOX-induced cardiotoxicity; mechanism exploration and biomarkers screening were also conducted. Twelve mice were randomly divided into two groups, induction group was treated with doxorubicin, and the control group was given an equal quantity of saline. After the confirmation of myocardial injury in induction group, the heart tissues from both groups were isolated for RNA high-throughput sequencing. The expression profiles were compared between the two groups; a total of 295 mRNAs and 11 circRNAs were shown as biased expression in DOX-induced cardiotoxicity mouse hearts. The dysregulation of three circRNAs were validated by quantitative real-time PCR: mmu_circ_0015773, mmu_circ_0002106, and mmu_circ_001606. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the differentially expressed RNAs were performed; the results implied that DOX might cause cardiotoxicity by interfering hemoglobin-based oxygen delivery and DNA-associated signal pathways. We integrated the differential expressed mRNA and validated circRNAs by constructing a competing endogenous RNA (ceRNA) network, which indicated that the alteration of the three circRNAs could activate apoptosis process of myocardial cells. This study provided novel insight into the mechanisms of DOX induced cardiotoxicity, and potential biomarkers or therapeutic targets were also proposed.     

ceRNA调控miR-145-5p介导肿瘤发生发展的研究进展

miR-145-5p是一种微小RNA分子,基因定位于染色体5q32.1,参与恶性肿瘤的发生发展。竞争性内源RNA(competing endogenous RNA,ceRNA)与mRNA竞争结合miRNA结合位点,进而调控miRNA的作用,可能参与调控肿瘤的生物学特性。因此,本文就ceRNA靶向调控miRNA-145-5p与肿瘤的发生发展作一综述。     

基于lncRNA-mRNA网络识别高血压相关的lncRNA及其功能

目的 高血压是最常见的慢性病,也是心脑血管病最主要的危险因素,很多长链非编码RNA(long noncoding RNA,lncRNA)在心血管系统中具有重要作用.然而在高血压中lncRNA的研究却很缺乏.本课题的目的是识别高血压疾病相关的lncRNA并研究其在高血压中的功能,进而为高血压机制研究提供更多信息.方法 通过ceRNA理论构建全局lncRNA-mRNA网络.首先从GEO数据库中下载高血压疾病表达谱进行重注释,进而识别高血压相关差异表达基因和lncRNA,将其映射到全局lncRNA-mRNA网络上获得高血压特异的lncRNA-基因网络.对该网络拓扑性质进行分析得到高血压相关的lncRNA.对于高血压相关lncRNA,将其在高血压相关网络中所连接的基因用DAVID工具进行通路富集分析,预测高血压相关lncRNA的功能.结果 构建了高血压特异的lncRNA-基因网络(58个lncRNA、431个基因及4737条边).通过对其拓扑性质分析识别了在高血压中发挥非常重要作用的lncRNA:MALAT1,研究发现MALAT1可能通过TNF信号通路、MAPK信号通路来发挥其调控功能.结论 lncRNA MALAT1在高血压疾病中扮演重要作用,其可能通过TNF信号通路、MAPK信号通路来发挥其调控功能.