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[文章]

ceRNA在人类癌症中的研究(三)

RNA专题

关键词ceRNA、人、癌症

  

中文题目:综合分析显示多个长非编码rna及其在食管鳞状细胞癌进展中的潜在作用

英文题目:Li CY, Zhang WW, Xiang JL, Wang XH, Wang JL, Li J. Integrated analysis highlights multiple long non‑coding RNAs and their potential roles in the progression of human esophageal squamous cell carcinoma.[J]. Oncology Reports, 2019, 42(6):2583-2599.

  名:Oncology Reports     发表时间:2019.09      IF3.041

作者单位兰州大学

文章类型:报告类

 

英文摘要

Esophageal squamous cell carcinoma (ESCC) is a prevalent aggressive malignant tumor with poor prognosis. Investigations into the molecular changes that occur as a result of the disease, as well as identification of novel biomarkers for its diagnosis and prognosis, are urgently required. Long non-coding RNAs (lncRNAs) have been reported to play a critical role in tumor progression. The present study performed data mining analyses for ESCC via an integrated study of accumulated datasets and identification of the differentially expressed lncRNAs from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The identified intersection of differentially expressed genes (lncRNAs, miRNAs and mRNAs) in ESCC tissues between the GEO and TCGA datasets was investigated. Based on these intersected lncRNAs, the present study constructed a competitive endogenous RNA (ceRNA) network of lncRNAs in ESCC. A total of 81 intersection lncRNAs were identified; 67 of these were included in the ceRNA network. Functional analyses revealed that these 67 key lncRNAs primarily dominated cellular biological processes. The present study then analyzed the associations between the expression levels of these 67 key lncRNAs and the clinicopathological characteristics of the ESCC patients, as well as their survival time using TCGA. The results revealed that 31 of these lncRNAs were associated with tumor grade, tumor-node-metastasis (TNM) stage and lymphatic metastasis status (P<0.05). In addition, 15 key lncRNAs were demonstrated to be associated with survival time (P<0.05). Finally, 5 key lncRNAs were selected for validation of their expression levels in 30 patients newly diagnosed with ESCC via reverse transcription-quantitative PCR (RT-qPCR). The results suggested that the fold changes in the trends of up-and downregulation between GEO, TCGA and RT-qPCR were consistent. In addition, it was also demonstrated that a select few of these 5 key lncRNAs were significantly associated with TNM stage and lymph node metastasis (P<0.05). The results of the clinically relevant analysis and the aforementioned bioinformatics were similar, hence proving that the bioinformatics analysis used in the present study is credible. Overall, the results from the present study may provide further insight into the functional characteristics of lncRNAs in ESCC through bioinformatics integrative analysis of the GEO and TCGA datasets, and reveal potential diagnostic and prognostic biomarkers for ESCC. 

 

中文摘要

食管鳞状细胞癌(ESCC)是一种常见的侵袭性恶性肿瘤,预后差。目前迫切需要对该病的分子变化进行研究,并为其诊断和预后鉴定新的生物标志物。据报道,lncRNAs在肿瘤发展中起着重要作用。本研究通过对累积数据集的综合研究以及从基因表达总集(GEO)和癌症基因组图谱(TCGA)数据库中识别差异表达的lncRNAs,对ESCC进行数据挖掘分析。研究了GEOTCGA数据集之间ESCC组织中差异表达基因(lncRNAsmiRNAsmRNAs)的交叉点。基于这些交叉的lncRNAs,本研究构建了一个竞争性内源性RNAceRNA)网络。共识别出81个交叉的lncRNAs,其中67个包含在ceRNA网络中。功能分析显示,这67个关键的lncRNA主要参与细胞生物学过程。本研究分析了67个关键lncRNA的表达水平与ESCC患者的临床病理特征以及TCGA治疗后生存时间的关系。结果显示,31个lncRNA与肿瘤分级、肿瘤淋巴结转移(TNM)分期及淋巴结转移状态有关(P<0.05)。此外,15个关键的lncRNA与生存时间相关(P<0.05)。最后,选择5个关键的lncRNA,通过逆转录定量PCRRT-qPCR)对30例新诊断为ESCC的患者的表达水平进行验证。结果表明,GEOTCGART-qPCR之间的升降调节趋势具有一致性。另外,5种关键性lncRNA中的少数与TNM分期和淋巴结转移有显著相关性(P<0.05)。临床相关分析结果与上述生物信息学结果相似,证明本研究所用的生物信息学分析是可信的。总之,本研究的结果可以通过对GEOTCGA数据集的生物信息学综合分析,进一步了解lncRNAs在食管鳞癌中的功能特点,揭示食管鳞癌的潜在诊断和预后生物标志物

 

 

中文题目:通过miR-646/VAMP2miR-647/MDM2信号通路上调环状RNA circ-FAM53B预测卵巢癌的不良预后并加速其进展

英文题目:Sun D, Liu J, Zhou L. Upregulation of circular RNA circ-FAM53B predicts adverse prognosis and accelerates the progression of ovarian cancer via the miR-646/VAMP2 and miR-647/MDM2 signaling pathways[J]. Oncology Reports, 2019, 42(6):2728-2737.

  名:Oncology Reports     发表时间:2019.9     IF3.041

作者单位黑龙江省医院

文章类型:研究类

 

英文摘要

Ovarian cancer (OC) is a common cancer of the human genital system. Circular RNAs (circRNAs) play an important role in carcinogenesis and progression of various cancers. The present study aimed to clarify the expression profile and functions of circ-FAM53B in the progression of OC and reveal its underlying mechanisms. Relative levels of circ-FAM53B in OC specimens and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The clinical significance of circ-FAM53B in OC patients was analyzed through Fisher\'s exact test, Kaplan-Meier curves, and Cox regression analysis. Subsequently, the regulatory effects of circ-FAM53B on the proliferative, apoptotic, migratory, and invasive potential of OC cells were determined by loss/gain-of-function experiments. Mechanistically, bioinformatics analysis and luciferase reporter gene assay were used to reveal the potential molecular mechanisms of circ-FAM53B in OC. Circ-FAM53B was overexpressed in OC specimens and cells and correlated with clinical severity and poor prognosis of OC patients. The overexpression of circ-FAM53B accelerated the proliferation, migration, and invasion of HO8910 cells; however, it decreased the number of apoptotic cells. Silencing of circ-FAM53B induced the opposite effect. Through dual-luciferase reporter gene assay and functional experiments, the potential functions of circ-FAM53B/miRNA-646/vesicle-associated membrane protein 2 (VAMP2) and circ-FAM53B/miRNA-647/mouse double minute 2 (MDM2) in mediating the progression of OC were identified. Collectively, the present results indicated that circ-FAM53B could be a competing endogenous RNA (ceRNA) to competitively sponge miR-646 and miR-647 to upregulate VAMP2 and MDM2 expression at the post-transcriptional level, thus mediating the cellular behaviors of OC cells.

 

中文摘要:

卵巢癌(OC)是人类生殖系统常见的癌症。circRNAs在多种癌症的发生、发展中起着重要作用。本研究旨在阐明circ-FAM53BOC发生发展过程中的表达谱和功能,并揭示其潜在机制。采用定量实时聚合酶链反应(qRT-PCR)检测OC标本和细胞株中circ-FAM53B的相对水平。采用Fisher精确检验、Kaplan-Meier曲线、Cox回归分析等方法,分析卵巢癌患者circ-FAM53B的临床意义。随后,通过功能丧失/获得实验确定circ-FAM53BOC细胞增殖、凋亡、迁移和侵袭潜能的调节作用。从机理上,利用生物信息学分析和荧光素酶报告基因分析揭示了circ-FAM53BOC中的潜在分子机制。卵巢癌标本和细胞中circ-FAM53B的高表达与临床严重程度和预后不良有关。circ-FAM53B的过度表达加速了HO8910细胞的增殖、迁移和侵袭,但减少了凋亡细胞的数量。circ-FAM53B的沉默诱导了相反的效应。通过双荧光素酶报告基因分析和功能实验,鉴定了circ-FAM53B/miRNA-646/囊泡相关膜蛋白2VAMP2)和circ-FAM53B/miRNA-647/小鼠双分钟2MDM2)在介导OC进展中的潜在功能。总之,本研究结果表明,circ-FAM53B可能是一种竞争性内源性RNAceRNA),竞争性地在转录后水平上调VAMP2MDM2的表达,从而介导OC细胞的细胞行为。

 

 

中文题目:LncRNA OsE1-AS1通过调控miR-32-3p/Rab23促进肝癌的发生

英文题目:Fan J, Zhang J, Huang S, Li P. lncRNA OSER1-AS1 acts as a ceRNA to promote tumorigenesis in hepatocellular carcinoma by regulating miR-372-3p/Rab23 axis[J]. Biochemical and Biophysical Research Communications, 2019, pii: S0006-291X(19)32007-8.

  名:Biochemical and Biophysical Research Communications     发表时间:2019.10     IF2.705

作者单位河北化工医药高等专科学校

文章类型:研究类

 

英文摘要

Long non-coding RNAs (lncRNAs) are crucial regulators of tumorigenesis and progression in human cancer, including hepatocellular carcinoma (HCC). However, the role of most lncRNAs that are dysregulated in HCC remains to be elucidated. Here, we investigated the role of OSER1-AS1 in the progression of HCC. The results of database and qRT-PCR analysis demonstrated that OSER1-AS1 was highly expressed in HCC tissues and the high expression of OSER1-AS1 was closely associated with larger tumor size, advanced tumor stages, lower disease free survival and overall survival of HCC patients. OSER1-AS1 knockdown significantly inhibited the proliferation, invasion and migration of HCC cells, and induced the apoptosis. In addition, the dual luciferase reporter assay directly demonstrated that OSER1-AS1 functioned as a molecular sponge for miR-372-3p to promote Rab23 expression. Moreover, the results of immunohistochemistry and western blot analysis showed that Rab23 was highly expressed in HCC tissues, and the high expression of Rab23 was closely associated with the poor overall survival of HCC patients. Immunofluorescence assay also found the subcellular localization of Rab23 in HCC cells. Rab23 was obviously downregulated in cells that were transfected with miR-372-3p mimics. MiR-372-3p mimics significantly inhibited the proliferation and invasion of HCC cells). Rab23 restoration partially reversed miR-372-3p-induced tumor suppressive effects on HCC cells. In conclusion, we found that OSER1-AS1 acted as a ceRNA to sponge miR-372-3p, thereby positively regulating the Rab23 expression and ultimately acting as a tumor suppressor gene in HCC progression.

 

中文摘要

lncRNAs是包括肝细胞癌(HCC)在内的人类肿瘤发生和发展的重要调控因子。然而,大多数在肝癌中失调的lncRNA的作用仍有待阐明。在此,我们研究了OSER1-AS1在肝癌进展中的作用。数据库和qRT-PCR分析结果表明OSER1-AS1在肝癌组织中高表达,OSER1-AS1的高表达与肿瘤大小、肿瘤分期、无病生存率和肝癌患者的总体生存率密切相关。OSER1-AS1基因敲除显著抑制肝癌细胞的增殖、侵袭和迁移,并诱导肝癌细胞凋亡。此外,双荧光素酶报告法直接证明OSER1-AS1作为miR-372-3p的分子海绵,可以促进Rab23的表达。免疫组化和western blot分析结果显示,Rab23在肝癌组织中高表达,且Rab23的高表达与肝癌患者总体生存率低密切相关。免疫荧光法还发现Rab23在肝癌细胞中的亚细胞定位。在转染miR-372-3p-mimics的细胞中,Rab23明显下调。MiR-372-3p可明显抑制肝癌细胞的增殖和侵袭。Rab23修复部分逆转miR-372-3p对肝癌细胞的抑制作用。综上所述,我们发现OSER1-AS1作为一个ceRNA,对miR-372-3p起到海绵状作用,从而对Rab23的表达起到积极的调节作用,并最终在HCC的进展中起到抑癌基因的作用。

 

 

中文题目:LncRNA HCP5作为ceRNA应答miR-17-5pmiR-27a/b,通过MAPK信号通路调控儿童肥胖的发病机制

英文题目:Chen R, Xin G, Zhang X. Long non-coding RNA HCP5 serves as a ceRNA sponging miR-17-5p and miR-27a/b to regulate the pathogenesis of childhood obesity via the MAPK signaling pathway[J]. Journal of Pediatric Endocrinology & Metabolism, 2019.

  名:Molecular Therapy Nucleic Acids     发表时间:2019.10     IF1.239

作者单位:吉林大学中日联合医院

文章类型:研究类

 

英文摘要

Background: This study aimed to investigate the completing endogenous RNA (ceRNA) network involved in childhood obesity.

Methods: The microarray dataset GSE9624 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed long non-coding RNAs (lncRNAs) (DELs) and messenger RNAs (DEMs) were isolated between the childhood obesity and non-obesity tissue samples. Then, Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of isolated DEMs were performed. DELs and DEMs targeted miRNAs were predicted to construct a ceRNA regulatory network. Finally, critical lncRNAs were validated in another dataset.

Results: A total of 1257 differentially expressed RNAs were screened, including 28 lncRNAs and 1229 mRNAs. In addition, these RNAs were mainly involved in defense response, cell cycle, mitogen-activated protein kinase (MAPK) signaling pathway, apoptosis, etc. Three lncRNAs (human leukocyte antigen complex 5 [HCP5], long intergenic non-protein coding RNA 839 [LINC00839] and receptor activity modifying protein 2 [RAMP2-AS1]) and two related miRNAs (hsa-miR-17-5p and hsa-miR-27a/b-3p) were identified as key RNAs in childhood obesity. Specifically, lncRNA HCP5 interacted with miR-17-5p and miR-27a/b to regulate nemo-like kinase (NLK) and Ras-related protein 2 (RRAS2) via the MAPK signaling pathway. Finally, four genes (RRAS2, NLK, bcl2/adenovirus E1B protein-interacting protein 3 [BNIP3] and phorbol-12-myristate-13-acetate-induced protein 1 [PMAIP1]) targeted by miRNAs were predicted as critical genes and might be novel diagnostic biomarkers of childhood obesity.

Conclusions: lncRNA HCP5 could serve as a ceRNA sponging miR-17-5p and miR-27a/b to regulate the pathogenesis of childhood obesity via NLK and RRAS2 in the MAPK signaling pathway.

 

中文摘要

背景本研究旨在探讨儿童肥胖与ceRNA网络的关系。

方法从基因表达综合数据库(GEO)中下载基因芯片GSE9624。从儿童肥胖和非肥胖组织中分离到差异表达的lncRNAsDELsmRNADEMs)。然后,对DEMs进行基因本体(GO)功能分析和KEGG途径分析。以DELsDEMs为靶点的miRNAs有望构建一个ceRNA调控网络。最后,在另一个数据集中验证了关键的lncRNA

结果共筛选出1257个差异表达RNA,其中28lncRNA1229mRNA。此外,这些RNA主要参与防御反应、细胞周期、丝裂原活化蛋白激酶(MAPK)信号通路、细胞凋亡等,长基因间非蛋白编码RNA 839[linc0839]和受体活性修饰蛋白2[RAMP2-AS1])以及两个相关的miRNAhsa-miR-17-5phsa-miR-27a/b-3p)被认为是儿童肥胖的关键RNA。具体来说,lncRNA HCP5通过MAPK信号途径与miR-17-5pmiR-27a/b相互作用,调节nemo样激酶(NLK)和Ras相关蛋白2RRAS2)。最后,以miRNAs为靶点的4个基因(RRAS2NLKbcl2/腺病毒E1B蛋白相互作用蛋白3[BNIP3]phorbol-12-肉豆蔻酸-13-醋酸诱导蛋白1[PMAIP1])被预测为儿童肥胖症的关键基因,可能成为儿童肥胖症的新的诊断标志物。

结论:lncRNA HCP5可通过MAPK信号通路中的NLKRRAS2,作为一种受体介导miR-17-5pmiR-27a/b调控儿童肥胖的发病机制。

 

 

中文题目:多发性骨髓瘤患者lncRNA的全基因组发现与鉴定

英文题目:Lu M, Hu Y, Wu Y, Zhou H, Jian Y, Tian Y, Chen W. Genome-wide discovery and characterization of long noncoding RNAs in patients with multiple myeloma[J]. BMC Med Genomics, 2019.

  名:BMC Med Genomics     发表时间:2019.10     IF2.568

作者单位:北京朝阳医院

测序项目:全转录组链特异性RNA测序

样品来源:

文章类型:研究类

 

英文摘要

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM. METHODS: In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified. RESULTS: The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer-associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development. CONCLUSIONS: Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.

 

中文摘要

背景:lncRNAs参与了肿瘤发生的多种生物学过程。然而,lncRNA的表达在人类多发性骨髓瘤(MM生物学、预后和分子分类中的作用尚不清楚,尤其是绝大多数lncRNA的生物学功能。近年来,lncRNAs已在肿瘤性血液病中被发现。有关lncRNAs作用的分子机制的证据为深入了解其在肿瘤发生中的功能作用提供了线索。本研究旨在探讨MM患者潜在的LncRNA

方法:对3例初诊MM患者进行全转录组链特异性RNA测序。并对整个转录组,包括lncRNAsmicroRNAsmRNAs都进行分析。利用这些数据,对MM-lncRNAs进行了系统的分析,并对MM发生中涉及的lncRNAs进行了鉴定。

结果:MM-lncRNAs具有与其他恶性肿瘤不同的特征。进一步验证了一组优先表达于MMLncRNA的功能,并鉴定了几个LncRNA为竞争性内源性RNA。更重要的是,某些LncRNA的异常表达,包括母系表达的gene3、结肠癌相关转录本1和包含26的卷曲螺旋结构域,以及一些参与MM发生的新的LncRNA被建立。此外,lncRNAs与一些microRNAs相关,相互调节,参与MM的发育。

结论:全基因组筛选和功能分析有助于鉴定与MM发生有关的一组LncRNAmicroRNAsLncRNAs之间的相互作用

 

 

Hello ATCG 2019-11-27 18:11:04

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