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[文章]

ceRNA在人类癌症中的研究(一)

RNA专题

关键词ceRNA、人、癌症

 

中文题目:lncRNA H19与癌症:一种竞争性内源性RNA

英文题目:Ye Y, Shen A, Liu A. Long non-coding RNA H19 and cancer: A competing endogenous RNA.[J]. Bulletin du Cancer, 2019, pii: S0007-4551(19)30327-3.

 

  名:Bulletin du Cancer   发表时间:2019.11   IF0.729

作者单位南昌大学

文章类型:综述类

 

英文摘要

Long non-coding RNA (lncRNA) is a class of non-coding RNA with a length of more than 200 nucleotides, which has become a hotspot in the research of tumorigenesis and development in recent years. Accumulating studies have indicated that H19 is abnormally expressed in human malignant tumors, and regulates cell proliferation, migration, invasion, anti-apoptosis and epithelial-mesenchymal transition through various mechanisms, thus playing a carcinogenic or anti-cancer role. H19 has been found to act as a microRNA sponge to indirectly regulate the expression of microRNA downstream target genes thus mediating cancer progression in several cancer types. Even in the same cancer, H19 also sponges various microRNAs to mediate diverse regulatory mechanisms. Tissue-specific expression of H19 suggests that it may be an early diagnostic marker or prognostic indicator of cancers. In this review, we summarize the latest original researches, mainly focusing on the role of H19 sponging microRNAs in cancers. We hope this article can facilitate readers obtain the molecular mechanisms of H19 sponging miRNAs in cancers and provide a broad perspective for further research on cancer diagnosis and therapy.

 

中文摘要

lncRNA是一类长度超过200个核苷酸的非编码RNA,近年来已成为肿瘤发生发展研究的热点。大量研究表明,H19在人类恶性肿瘤中异常表达,并通过多种机制调节细胞增殖、迁移、侵袭、抗凋亡和上皮间充质转化,从而发挥致癌或抗癌作用。H19被发现作为microRNA海绵,间接调节microRNA下游靶基因的表达,从而介导多种癌症类型的癌症进展。即使是在同一种癌症中,H19也可以利用不同的microRNAs介导不同的调节机制。H19的组织特异性表达提示它可能是癌症的早期诊断标志或预后指标。本文综述了近年来的最新研究成果,主要集中在H19应答的microRNAs在肿瘤中的作用。希望本文能帮助读者了解H19在肿瘤中的分子机制,为进一步研究肿瘤的诊断和治疗提供广阔的前景

 

 

中文题目:长非编码RNA HCP5作为miR-4656的海绵调节CEMIP表达促进前列腺癌细胞增殖

英文题目:Hu R, Lu Z. Long non‑coding RNA HCP5 promotes prostate cancer cell proliferation by acting as the sponge of miR-4656 to modulate CEMIP expression[J]. Oncology Reports, 2019.

 

  名:Oncology Reports   发表时间:2019.11   IF3.041

作者单位汉川人民医院

样品来源:

文章类型:研究型

 

英文摘要

Aberrant expression of long noncoding RNAs (lncRNAs) has been demonstrated in human cancers and regulates the malignant behavior of cancer cells. Previous studies demonstrated the critical involvement of lncRNA histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in the development of cancers, however, the function of HCP5 in prostate cancer has not been reported. In the present study, we found the overexpressed expression of HCP5 in prostate cancer tissues and cell lines via RTqPCR analysis. High expression of HCP5 was positively correlated with the metastasis of prostate cancer. Downregulation of HCP5 inhibited the proliferation, colony formation and induced apoptosis of prostate cancer cells. Functional experiments demonstrated that HCP5 acted as a competing endogenous RNA (ceRNA) to sponge miR4656. Ectopic expression of HCP5 decreased the expression of miR4656 in prostate cancer cells. MiR4656 was found to be decreased in prostate cancer tissues and was negatively correlated with the expression of HCP5. Further luciferase reporter assay revealed that miR4656 was able to bind the 3\'untranslated region (3\'UTR) of the cell migration inducing hyaluronidase 1 (CEMIP) and suppressed the expression of CEMIP. Consistent with the negative regulation of miR4656 by HCP5, western blot analysis uncovered that overexpression of HCP5 upregulated the abundance of CEMIP in prostate cancer cells. The CCK8 assay showed that depletion of CEMIP significantly inhibited the HCP5promoted proliferation of prostate cancer cells. Collectively, our data provide a novel mechanism by which HCP5 regulates the progression of prostate cancer.

 

中文摘要

lncRNAs在人类肿瘤中的异常表达已被证实,调节着肿瘤细胞的恶性行为。以往的研究表明,lncRNA组织相容性白细胞抗原(HLA)复合物P5HCP5)在前列腺癌的发生发展中起重要作用,但HCP5在前列腺癌中的作用尚未见报道。在本研究中,我们通过RT-qPCR分析发现HCP5在前列腺癌组织和细胞系中过度表达。HCP5的高表达与前列腺癌的转移呈正相关。HCP5下调可抑制前列腺癌细胞增殖、集落形成和诱导凋亡。功能实验表明HCP5作为竞争性内源性RNAceRNA)对miR-4656具有吸附作用。HCP5的异位表达降低了前列腺癌细胞miR-4656的表达。miR-4656在前列腺癌组织中表达降低,与HCP5表达呈负相关。进一步的荧光素酶报告分析显示miR-4656能够结合诱导细胞迁移的透明质酸酶1CEMIP)的3\'-非翻译区(3\'-UTR),并抑制CEMIP的表达。与HCP5miR-4656的负调控一致,western blot分析发现HCP5的过度表达上调了前列腺癌细胞中CEMIP的含量。CCK-8检测显示,CEMIP的缺失显著抑制HCP5促进的前列腺癌细胞增殖。总的来说,我们的数据提供了一个新的机制,即HCP5调节前列腺癌的展。

 

 

中文题目:肝细胞癌关键基因和长非编码RNA相关ceRNA网络的鉴定

英文题目:Liu J, Li W, Zhang J, Ma Z, Wu X, Tang L. Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma[J]. PeerJ, 2019, 7:e8021.

 

  名:Oncology Reports   发表时间:2019.11   IF3.041

作者单位韶关粤北人民医院

样品来源:

文章类型:研究型

 

英文摘要

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although multiple efforts have been made to understand the development of HCC, morbidity, and mortality rates remain high. In this study, we aimed to discover the mRNAs and long non-coding RNAs (lncRNAs) that contribute to the progression of HCC. We constructed a lncRNA-related competitive endogenous RNA (ceRNA) network to elucidate the molecular regulatory mechanism underlying HCC. 

Methods: A microarray dataset (GSE54238) containing information about both mRNAs and lncRNAs was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) in tumor tissues and non-cancerous tissues were identified using the limma package of the R software. The miRNAs that are targeted by DElncRNAs were predicted using miRcode, while the target mRNAs of miRNAs were retrieved from miRDB, miRTarBas, and TargetScan. Functional annotation and pathway enrichment of DEGs were performed using the EnrichNet website. We constructed a protein-protein interaction (PPI) network of DEGs using STRING, and identified the hub genes using Cytoscape. Survival analysis of the hub genes and DElncRNAs was performed using the gene expression profiling interactive analysis database. The expression of molecules with prognostic values was validated on the UALCAN database. The hepatic expression of hub genes was examined using the Human Protein Atlas. The hub genes and DElncRNAs with prognostic values as well as the predictive miRNAs were selected to construct the ceRNA networks. 

Results: We found that 10 hub genes (KPNA2, MCM7, CKS2, KIF23, HMGB2, ZWINT, E2F1, MCM4, H2AFX, and EZH2) and four lncRNAs (FAM182B, SNHG6, SNHG1, and SNHG3) with prognostic values were overexpressed in the hepatic tumor samples. We also constructed a network containing 10 lncRNA-miRNA-mRNA pathways, which might be responsible for regulating the biological mechanisms underlying HCC.

Conclusion: We found that the 10 significantly overexpressed hub genes and four lncRNAs were negatively correlated with the prognosis of HCC. Further, we suggest that lncRNA SNHG1 and the SNHG3-related ceRNAs can be potential research targets for exploring the molecular mechanisms of HCC.

 

中文摘要

背景:肝细胞癌(Hepatocellular carcinomaHCC)是世界范围内导致癌症相关死亡的主要原因之一。尽管已经做出了多方面的努力来了解肝癌的发展,发病率和死亡率仍然很高。在这项研究中,我们旨在发现参与肝癌的mRNAslncRNAs。我们构建了一个与lncRNA相关的竞争性内源性RNAceRNA)网络来阐明HCC的分子调控机制。

方法:从基因表达综合数据库中下载包含mRNAslncRNAs信息的微阵列数据集(GSE54238)。利用R软件的limma软件包对肿瘤组织和非癌组织中的差异表达基因(DEGs)和lncRNAsDElncRNAs)进行了鉴定。使用miRcode预测DElncRNAs靶向的miRNAs,从miRDBmiRTarBasTargetScan检索miRNAs靶向的mRNA。使用EnrichNet网站对DEGs进行功能注释和路径富集。我们利用STRING构建了DEGs的蛋白质-蛋白质相互作用(PPI)网络,并利用Cytoscape鉴定了hub基因。利用基因表达谱交互分析数据库对hub基因和DElncRNAs进行生存分析。具有预后价值的分子的表达在UALCAN数据库中得到验证。用人类蛋白质图谱检测hub基因在肝脏的表达。选择具有预测价值的hub基因和DElncRNAs以及具有预测价值的miRNAs构建ceRNA网络。

结果:我们发现10个具有预后价值的hub基因(KPNA2MCM7CKS2KIF23HMGB2ZWINTE2F1MCM4H2AFXEZH2)和4lncrnaFAM182BSNHG6SNHG1SNHG3)在肝肿瘤中高表达。我们还构建了一个包含10lncRNA-miRNA通路的网络,可能负责调控肝癌的生物学机制。

结论:10hub基因和4lncrna显著表达与HCC预后呈负相关。此外,我们认为lncRNA SNHG1SNHG3相关的ceRNAs可能是探索肝癌分子机制的潜在研究目标。

 

 

中文题目:上调LncRNA Malat1通过miR-150-eIF4E/Akt信号诱导气道平滑肌细胞增殖和迁移

英文题目:Lin , Li Q, Hao W, Zhang Y, Zhao L Han W. Upregulation of LncRNA Malat1 Induced Proliferation and Migration of Airway Smooth Muscle Cells via miR-150-eIF4E/Akt Signaling[J]. Frontiers in Physiology, 2019, 10:1337.

 

  名:Frontiers in Physiology   发表时间:2019.10   IF3.201

作者单位青岛市市立医院

样品来源:

文章类型:研究型

 

英文摘要

The increased proliferation and migration of airway smooth muscle cells (ASMCs) are critical processes in the formation of airway remodeling in asthma. Long non-coding RNAs (lncRNAs) have emerged as key mediators of diverse physiological and pathological processes, and are involved in the pathogenesis of various diseases, including asthma. LncRNA Malat1 has been widely reported to regulate the proliferation and migration of multiple cell types and be involved in the pathogenesis of various human diseases. However, it remains unknown whether Malat1 regulates ASMC proliferation and migration. Here, we explored the function of Malat1 in ASMC proliferation and migration in vitro stimulated by platelet-derived growth factor BB (PDGF-BB), and the underlying molecular mechanism involved. The results showed that Malat1 was significantly upregulated in ASMCs treated with PDGF-BB, and knockdown of Malat1 effectively inhibited ASMC proliferation and migration induced by PDGF-BB. Our data also showed that miR-150 was a target of Malat1 in ASMCs, and inhibited PDGF-BB-induced ASMC proliferation and migration, whereas the inhibition effect was effectively reversed by Malat1 overexpression. Additionally, translation initiation factor 4E (eIF4E), an important regulator of Akt signaling, was identified to be a target of miR-150, and both eIF4E knockdown and Akt inhibitor GSK690693 inhibited PDGF-BB-induced ASMC proliferation and migration. Collectively, these data indicate that Malat1, as a competing endogenous RNA (ceRNA) for miR-150, derepresses eIF4E expression and activates Akt signaling, thereby being involved in PDGF-BB-induced ASMC proliferation and migration. These findings suggest that Malat1 knockdown may present a new target to limit airway remodeling in asthma. 

 

中文摘要

道平滑肌细胞(ASMCs)的增殖和迁移是哮喘气道重塑形成的关键过程。lncRNAs是多种生理和病理过程的关键介质,参与了包括哮喘在内的多种疾病的发病机制。LncRNA Malat1被广泛报道调节多种细胞类型的增殖和迁移,并参与多种人类疾病的发病机制。然而,目前尚不清楚Malat1是否调节ASMC的增殖和迁移。本研究探讨了Malat1在血小板源性生长因子BBPDGF-BB)体外诱导的ASMC增殖和迁移中的作用及其分子机制。结果表明,经PDGF-BB处理的ASMCsMalat1显著上调,Malat1基因敲除可有效抑制PDGF-BB诱导的ASMC增殖和迁移。我们的数据还显示miR-150ASMCsMalat1的靶点,并且抑制PDGF-BB诱导的ASMC增殖和迁移,而Malat1的过度表达有效地逆转了这种抑制作用。此外,翻译起始因子4EeIF4E)是Akt信号的重要调节因子,被认为是miR-150的靶点,eIF4E基因敲除和Akt抑制剂GSK690693均抑制PDGF-BB诱导的ASMC增殖和迁移。总之,这些数据表明,Malat1作为miR-150的竞争性内源性RNAceRNA),下调eIF4E的表达,激活Akt信号,从而参与PDGF-BB诱导的ASMC增殖和迁移。这些发现提示,Malat1基因敲除可能是限制哮喘气道重塑的新靶点。

 

 

中文题目:小鼠视网膜新生血管中circRNA相关ceRNA网络的识别

英文题目:Cao M, Zhang L, Wang JH, Zeng H, Peng Y, Zou J, Shi J, Zhang L, Li Y, Yoshida S, Tang L, Zhou Y. Identifying circRNA-associated-ceRNA networks in retinal neovascularization in mice[J]. International Journal of Medical Sciences, 2019, 16(10):1356-1365.

 

  名:International Journal of Medical Sciences 发表时间:2019.9   IF2.333

作者单位中南大学湘雅二院

样品来源:

文章类型:研究型

 

英文摘要

Retinal neovascularization is a complication which caused human vision loss severely. It has been shown that circular RNAs (circRNAs) play essential roles in gene regulation. However, circRNA expression profile and the underlying mechanisms in retinal neovascular diseases remain unclear. In the present study, we identified altered circRNAs in the retinas of oxygen-induced retinopathy (OIR) mouse model by microarray profiling. Microarray analysis revealed that 539 circRNAs were significantly altered in OIR retinas compared with controls. Among them, 185 up-regulated and 354 down-regulated circRNAs were identified. The expression levels of 4 altered circRNAs including mmu_circRNA_002573, mmu_circRNA_011180, mmu_circRNA_016108 and mmu_circRNA_22546 were validated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatic analysis with validated circRNAs such as competing endogenous RNA (ceRNA) regulatory networks with Gene Ontology (GO) enrichment analysis demonstrated that qRT-PCR validated circRNAs were associated with cellular process, cell part and phosphoric ester hydrolase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that MAPK signaling pathway and renin-angiotensin system were related to validated circRNAs, suggesting these pathways may participate in pathological angiogenesis. The results together suggested that circRNAs were aberrantly expressed in OIR retinas and may play potential roles in retinal neovascular diseases.

 

中文摘要:

视网膜新生血管是一种严重影响人类视力的并发症。已有研究表明,circRNAs在基因调控中起着重要作用。然而,视网膜新生血管疾病的circRNA表达谱及其机制尚不清楚。在本研究中,我们通过微阵列分析鉴定了氧诱导性视网膜病变(OIR)小鼠模型视网膜中的环状结构改变。微阵列分析显示,与对照组相比,OIR视网膜中539circRNAs显著改变。其中,共鉴定出185个上调和354个下调的circRNAs。定量实时逆转录聚合酶链反应(qRT-PCR)检测mmu-circRNA-002573mmu-circRNA-011180mmu-circRNA-016108mmu-circRNA-225464种基因的表达水平。利用ceRNA调控网络和基因本体(GO)富集分析等验证的circRNAs进行生物信息学分析表明,qRT-PCR验证的circRNAs与细胞过程、细胞部位和磷酸酯水解酶活性有关京都基因与基因组百科全书(KEGG)通路分析表明MAPK信号通路和肾素-血管紧张素系统与已证实的circRNAs相关,提示这些通路可能参与病理性血管生成。这些结果提示circRNAsOIR视网膜中异常表达,可能在视网膜新生血管疾病中发挥潜在作用。

 

Hello ATCG 2019-11-27 18:02:26

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