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ceRNA在人类癌症中的研究(二)

RNA专题

关键词ceRNA、人、癌症

 

 

中文题目:类癌症中的长非编码RNA TP73-AS1

英文题目:Chu F, Xue L, Miao H. Long noncoding RNA TP73-AS1 in human cancers[J]. Clinica Chimica Acta, 2019, pii: S0009-8981(19)32058-3.

 

  名:Clinica Chimica Acta     发表时间:2019.04      IF2.735

作者单位南通市肿瘤医院

文章类型:综述类

 

英文摘要

Long noncoding RNAs (lncRNAs) play an important role in tumor development. With the development of sequencing technology, many new lncRNAs have been discovered. lncRNA TP73-AS1 is abnormally expressed in many cancers. A summary of the current literature related to TP73-AS1 reveals that TP73-AS1 mainly regulates the occurrence and development of tumors through the mechanism of competitive endogenous RNA (ceRNA). In addition, the abnormal expression of TP73-AS1 can regulate the malignant function of tumor cells through a variety of possible mechanisms. All evidence suggests that TP73-AS1 may be a potential diagnostic biomarker or a new cancer therapeutic target

 

中文摘要

lncRNAs在肿瘤的发生发展中起着重要作用。随着测序技术的发展,人们发现了许多新的lncRNAlncRNA TP73-AS1在许多癌症中异常表达。与TP73-AS1相关的文献显示TP73-AS1主要通过竞争性内源性RNAceRNA)机制调控肿瘤的发生和发展。此外,TP73-AS1的异常表达可能通过多种机制调节肿瘤细胞的恶性功能。所有证据表明,TP73-AS1可能是一个潜在的诊断生物标志物或新的肿瘤治疗靶点

 

中文题目:BCL11B作为竞争性内源性RNA调节MICA/B介导的免疫应答

英文题目:Qian M, Geng J, Luo K, Huang Z, Zhang Q, Zhang JA, Ji L, Wu J. BCL11B regulates MICA/B-mediated immune response by acting as a competitive endogenous RNA[J]. Oncogene, 2019.

 

  名:Oncogene     发表时间:2019.10     IF6.634

作者单位温州医科大学

文章类型:研究类

 

英文摘要

Cancer immune surveillance is an important host protection process that inhibits carcinogenesis and maintains cellular homeostasis. The major histocompatibility complex class I-related molecules A and B (MICA and MICB) are NKG2D ligands that play important roles in tumor immune surveillance. In the present study, by a combined bioinformatics prediction and experimental approach, we identify BCL11B 3\'-UTR as a putative MICA and MICB ceRNA. We demonstrate in several human cell lines of different origins that the knockdown of BCL11B downregulates surface expression of MICA and MICB. Furthermore, we demonstrate miRNA dependency of BCL11B-mediated MICA and MICB regulation in Dicer knockdown HCT116 cells. In addition, MICA/B-targeting miRNAs (miR-17, miR-93, miR-20a, miR-20b, miR-106a, and miR-106b) repressed the expression of BCL11B by targeting its 3\'-UTR. Moreover, we showed that the BCL11B knockdown-mediated downregulation of MICA/B resulted in reduced NK cell elimination in vitro and in vivo through reduced recognition of NKG2D. Of particular significance, BCL11B displays tumor-suppressive properties. The expression of BCL11B is downregulated in colon cancer tissues and associated with a reduced median survival of colon cancer patients. Taken together, our study revealed a new mechanism of BCL11B that prevents immune evasion of cancerous cells by upregulation of the NKG2D ligands MICA and MICB in a ceRNA manner.

 

英文摘要:

肿瘤免疫监测是抑制肿瘤发生、维持细胞内稳态的重要宿主保护过程。主要组织相容性复合物I类相关分子ABMICAMICB)是NKG2D配体,在肿瘤免疫监测中发挥重要作用。在本研究中,通过生物信息学预测和实验相结合的方法,我们确定BCL11B 3\'-UTR是一种假定的MICAMICB-ceRNA。我们在几个不同来源的人细胞系中证明,BCL11B的敲除下调了MICAMICB的表达。此外,我们还证明了BCL11B介导的MICAmiRNA依赖性和DICE基因敲除HCT116细胞的MICB调节。此外,MICA/B靶向miRNAsmiR-17miR-93miR-20amiR-20bmiR-106amiR-106b)通过靶向其3\'-UTR抑制BCL11B的表达。此外,我们还发现,BCL11B基因敲除介导的MICA/B基因下调通过降低对NKG2D的识别而导致NK细胞在体内外的清除减少,特别是BCL11B具有抑瘤特性。BCL11B在结肠癌组织中的表达下调,与结肠癌患者的中位生存率降低有关。综上所述,我们的研究揭示了BCL11B的一种新机制,通过以ceRNA方式上调NKG2D配体MICAMICB来防止癌细胞的免疫逃避。

 

 

中文题目:Oct4介导的重编程诱导人成纤维细胞胚胎样microRNA表达

英文题目:Peskova L, Cerna K, Oppelt J, Mraz M, Barta T. Oct4-mediated reprogramming induces embryonic-like microRNA expression signatures in human fibroblasts[J]. Scientific Reports, 2019, 9(1):15759.

 

  名:Scientific Reports     发表时间:2019.10     IF4.011

作者单位马萨里克大学医学院

文章类型:研究类

 

英文摘要

Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically "open" state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.

 

中文摘要

Oct4介导的重编程已成为从分化的体细胞中产生各种细胞类型的新工具。尽管这一过程的分子机制尚不清楚,但有充分的证据表明过度表达Oct4的细胞经历了从分化状态到可塑状态的转变。这种转变与干细胞特性的获得有关,导致表观遗传的开放状态,允许细胞命运在外部刺激下转换。为了帮助我们理解驱动这一过程的分子机制,我们对过度表达Oct4的人成纤维细胞进行了表征,并进行了全面的RNA-seq分析。我们的分析揭示了Oct4介导的细胞可塑性诱导的新的方面。过度表达Oct4的细胞通过纤维细胞特异基因的下调和上皮基因的上调失去其细胞特性。有趣的是,这个过程与microRNA表达谱相关,microRNA表达谱与多能干细胞中常见的microRNA表达谱相似。我们还提供了广泛的microRNA家族和簇网络,使我们能够精确地确定与Oct4诱导的瞬态塑性状态获取相关的miRNAome。我们的数据扩展了目前关于microRNA及其在细胞命运改变中的意义的知识,并有助于理解其背后的分子机制。

 

 

中文题目:lncRNA ADAMTS9-AS2控制人骨髓间充质干细胞软骨分化并作为ceRNA发挥作用

英文题目:Huang MJ, Zhao JY, Xu JJ, Li J, Zhuang YF, Zhang XL. lncRNA ADAMTS9-AS2 Controls Human Mesenchymal Stem Cell Chondrogenic Differentiation and Functions as a ceRNA[J]. Molecular Therapy Nucleic Acids, 2019, 18:533-545.

 

  名:Molecular Therapy Nucleic Acids     发表时间:2019.9     IF5.919

作者单位:上海交通大学新华医院

文章类型:研究类

 

英文摘要

Long noncoding RNAs (lncRNAs) have emerged as key regulators of cell differentiation and development. However, potential roles for lncRNAs in chondrogenic differentiation have remained poorly understood. Here we identify lncRNA ADAMTS9 antisense RNA 2, ADAMTS9-AS2, which controls the chondrogenic differentiation by acting as a competing endogenous RNA (ceRNA) in human mesenchymal stem cells (hMSCs). We screen out ADAMTS9-AS2 of undifferentiated and differentiated cells during chondrogenic differentiation by microarrays. Suppression or overexpression of lncRNA ADAMTS9-AS2 correlates with inhibition and promotion of hMSC chondrogenic differentiation, respectively. We find that ADAMTS9-AS2 can sponge miR-942-5p to regulate the expression of Scrg1, a transcription factor promoting chondrogenic gene expression. Finally, we confirm the function of ADAMTS9-AS2 to cartilage repair in the absence of transforming growth factor β (TGF-β) in vivo. In conclusion, ADAMTS9-AS2 plays an important role in chondrogenic differentiation as a ceRNA, so that it can be regarded as a therapy target for cartilage repair.

 

中文摘要

lncRNAs已成为细胞分化和发育的关键调控因子。然而,lncRNAs在软骨细胞分化中的潜在作用仍不清楚。在这里我们鉴定了lncRNA-ADAMTS9反义RNA 2 ADAMTS9-AS2,它通过作为人类间充质干细胞(hMSCs)中的竞争性内源性RNAceRNA)来控制软骨的分化。我们用微阵列筛选出软骨分化过程中未分化和分化细胞的ADAMTS9-AS2lncRNA ADAMTS9-AS2的抑制或过度表达分别与抑制和促进hMSC软骨分化相关。我们发现ADAMTS9-AS2可以通过海绵状miR-942-5p调节Scrg1的表达,Scrg1是一种促进软骨生成基因表达的转录因子。最后,我们在体内证实了在没有转化生长因子βTGF-β)的情况下ADAMTS9-AS2对软骨修复的作用。总之,ADAMTS9-AS2作为ceRNA在软骨分化中起着重要的作用,因此可以作为软骨修复的治疗靶点。

 

 

中文题目:HR+/Her-2-乳腺癌和三阴性乳腺癌中miRNA-lncRNA-ceRNA网络的综合分析

英文题目:Jia X, Shi Y, Zhu Y, Meng W, He L, Jia Y, Tong Z. Integrated Analysis of mRNA-miRNA-lncRNA ceRNA Network in Human HR+/Her-2- Breast Cancer and Triple Negative Breast Cancer[J]. Journal of Computational Biology, 2019.

 

  名:Molecular Therapy Nucleic Acids     发表时间:2019.9     IF0.879

作者单位:天津医科大学肿瘤研究所

文章类型:研究类

 

英文摘要

Breast cancer is a heterogeneous disease highly diverse in different subtypes, including hormone receptor positive and hormone receptor negative subtypes with variable malignancy, therapy regimen, and different prognosis. In this study, we develop a hormone receptor-specific mRNA-miRNA-lncRNA ceRNA network to identify whether several RNAs play fundamental roles in development and metastasis of breast cancer. To understand the association of ceRNA expression profiles in different breast cancer subgroups, the expression profiles and clinical information of 428 HR+/Her-2- breast cancer samples and 113 triple negative breast cancer samples were downloaded from the Cancer Genome Atlas database (TCGA). We comprehensively integrated and compared expression profiles of mRNAs, miRNAs, and lncRNAs between the two subgroups mentioned. Aberrantly expressed hormone receptor specific RNAs were identified, whereas lncRNA-miRNA interactions predicted by miRcode and miRNA-targeted mRNA interactions were validated by miRTarBase, Targetscan, and miRDB database. In this study, mRNA-miRNA-lncRNA ceRNA network was constructed that consisted of 44 miRNA-lncRNA interaction pairs and 2 miRNA-mRNA interaction pairs, and visualized by Cytoscape software. Prognostic markers of HR-specific subtype of breast cancer associated with overall survival were identified by Kaplan-Meier survival analysis. Finally, SFRP1, AC006449.1, and MUC2 were novel clinical predictors that may also provide a new therapeutic target in the future.

 

中文摘要

乳腺癌是一种不同亚型高度分化的异质性疾病,包括激素受体阳性亚型和激素受体阴性亚型,恶性程度不同,治疗方案不同,预后不同。在这项研究中,我们开发了一个激素受体特异性的mRNA-miRNA-lncRNA-ceRNA网络,以确定几个RNA是否在乳腺癌的发生和转移中起着基础性作用。为了了解不同乳腺癌亚组中ceRNA表达谱的相关性,从肿瘤基因组图谱数据库(TCGA)下载了428HR+/Her-2乳腺癌和113例三阴性乳腺癌的表达谱和临床资料。我们综合比较了上述两个亚组间mRNAsmiRNAslncRNAs的表达谱。识别出异常表达的激素受体特异性RNA,而miRcode预测的lncRNA-miRNA相互作用和miRNA靶向mRNA相互作用通过miRTarBaseTargetscanmiRDB数据库验证。本研究构建了由44miRNA-lncRNA相互作用对和2miRNA-mRNA相互作用对组成的mRNA-lncRNA-ceRNA网络,并用Cytoscape软件进行可视化。Kaplan-Meier生存分析确定了与总生存率相关的乳腺癌HR特异性亚型的预后标志物。最后,SFRP1AC006449.1MUC2是新的临床预测因子,它们也可能在未来提供新的治疗靶点。

 

Hello ATCG 2019-11-27 18:06:27

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