circRNA作为ceRNA在转录调控中的研究(2)

  • 2019-12-09 13:28:07
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关键词:ceRNAcircRNAmiRNA

 

中文题目:CircRNA RNA_hsa_circ_000055作为miR-326海绵通过上调ELK1促进宫颈癌的进展

英文题目:Tang Q, Chen Z, Zhao L. Circular RNA hsa-circ-0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1[J]. Aging (Albany NY), 2019, 11(22):9982-9999.

 

  名:Aging (Albany NY)   发表时间:2019.11   IF5.515

作者单位华中科技大学同济医学院武汉市中心医院肿瘤科

分析项目:全转录组

样品来源:

文章类型:研究类

 

英文摘要

This study investigates the role of circular RNA (circRNA) hsa_circ_0000515 in cervical cancer and the underlying mechanism associated with microRNA-326 (miR-326). hsa_circ_0000515 and ETS transcription factor ELK1 (ELK1) were initially over-expressed and miR-326 was down-regulated in cervical cancer tissues and cells. Low hsa_circ_0000515 expression was found to be associated with favorable prognosis of patients with cervical cancer. A series of mimics, inhibitors, over-expression plasmids or siRNAs were introduced into cervical cancer cells to alter the expression of hsa_circ_0000515, miR-326 and ELK1. In vitro experiments exhibited that silencing of hsa_circ_0000515 or upregulation of miR-326 resulted in suppressed proliferation and invasion, along with induced apoptosis and autophagy of cervical cancer cells. Dual-luciferase reporter assay, RNA pull-down and RIP assays highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-326 to increase ELK1. Furthermore, enhancement of ELK1 expression resulted in enhanced proliferation and invasion but repressed apoptosis and autophagy of cervical cancer cells. In vivo experiments further confirmed the suppressed tumor growth by hsa_circ_0000515 silencing. Our findings demonstrated that hsa_circ_0000515 acts as a tumor promoter in cervical cancer. The study provides evidence for targeting hsa_circ_0000515 for therapeutic purposes in treating cervical cancer.

 

 

中文摘要

本研究探讨环状RNAcircRNAhsa-circ-u000055在宫颈癌中的作用及其与microRNA-326miR-326)相关的机制。hsa-circ-0000515ETS转录因子ELK1ELK1)最初在宫颈癌组织和细胞中过度表达,miR-326表达下调。hsa-circ-0000515的低表达与宫颈癌患者的良好预后有关。将一系列模拟物、抑制剂、过表达质粒或siRNAs导入宫颈癌细胞,改变hsa-circ-000055miR-326ELK1的表达。体外实验表明,hsa-u-circ-0000515的沉默或miR-326的上调可抑制宫颈癌细胞的增殖和侵袭,诱导其凋亡和自噬。双荧光素酶报告分析、RNA下拉和RIP分析表明hsa-circ-000055可以作为miR-326ceRNA增加ELK1。此外,ELK1的表达增强导致宫颈癌细胞的增殖和侵袭增强,但抑制细胞凋亡和自噬。体内实验进一步证实了hsa-circ-0000515沉默对肿瘤生长的抑制作用。我们的发现表明hsa-circ-u000055在宫颈癌中起着肿瘤启动子的作用。本研究为hsa-circ-0000515靶向治疗宫颈癌提供了依据。

 

 

 

中文题目:CircRNA-ENO1通过上调宿主基因ENO1促进肺腺癌糖酵解和肿瘤进展

英文题目:Zhou J, Zhang S, Chen Z, He Z, Xu Y, Li Z. CircRNA-ENO1 promoted glycolysis and tumor progression in lung adenocarcinoma through upregulating its host gene ENO1[J]. Cell Death Dis, 2019, 10(12):885.

 

  名:Cell Death Dis   发表时间:2019.11   IF5.959

作者单位浙江大学医学院邵逸夫医院

分析项目:全转录组

样品来源:

文章类型:研究型

 

英文摘要

Lung adenocarcinoma (LUAD) has long been one of the predominant reasons for the global cancer-linked mortality. The tumor progression is shown by several studies to be promoted by increased glycolysis. Enolase 1 (ENO1), as a glycolysis enzyme, performs pivotal role in glucose metabolism and contributes to tumor progression of numerous cancers. Circular RNAs (circRNAs) are catching increasing attentions for their surging roles in regulating gene expression in cancers. Our work is to uncover the regulatory mechanism circ-ENO1 on its host gene ENO1 and its function in glycolysis and tumor progression. Circ-ENO1 and its host gene ENO1 were identified to be upregulated in LUAD cells. Functionally, silencing circ-ENO1 retarded glycolysis, inhibited proliferation, migration and EMT, induced apoptosis. The cytoplasmic localization of circ-ENO1 was determined by FISH and subcellular fractionation. Mechanistically, circ-ENO1 acted as a ceRNA to interact with miR-22-3p and upregulate ENO1 expression. In vivo experiments certified that circ-ENO1 drove tumor growth and metastasis in vivo. In summary, current study elucidated that circ-ENO1 promoted glycolysis and tumor progression in LUAD by miR-22-3p/ENO1 axis, indicating circ-ENO1 as a promising treatment target for LUAD patients.

 

中文摘要

肺腺癌(LUAD)一直是全球癌症相关死亡率的主要原因之一。一些研究表明,糖酵解增加可促进肿瘤的进展。烯醇化酶1ENO1)作为一种糖酵解酶,在葡萄糖代谢中起着关键作用,并参与许多癌症的肿瘤进展。circRNAs在肿瘤基因表达调控中的作用日益受到人们的关注。我们的工作是揭示circ-ENO1对宿主基因ENO1的调控机制及其在糖酵解和肿瘤进展中的作用。Circ-ENO1及其宿主基因ENO1LUAD细胞中表达上调。在功能上,沉默circ-ENO1可延缓糖酵解,抑制细胞增殖、迁移和EMT,诱导细胞凋亡。circ-ENO1的胞质定位是通过FISH和亚细胞分离来确定的。在机制上,circ-ENO1作为ceRNAmiR-22-3p相互作用并上调ENO1的表达。体内实验证明circ-ENO1在体内促进肿瘤生长和转移。综上所述,目前的研究表明,CIRC-ENO-1通过miR2-23-3p/EnO1轴促进LUAD糖酵解和肿瘤进展,提示CIRC-ENO-1LUAD患者有前途的治疗靶点。

 

 

 

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:Yu AQ, Wang ZX, Wu W, Chen KY, Yan SR, Mao ZB. Circular RNA CircCCNB1 sponges micro RNA-449a to inhibit cellular senescence by targeting CCNE2[J]. Aging (Albany NY), 2019, 11(22):10220-10241.

 

  名:Aging (Albany NY)   发表时间:2019.11   IF5.515

作者单位北京大学

测序项目:全转录组测序

样品来源:

文章类型:研究型

 

英文摘要

Circular RNAs (CircRNAs) are a novel subset of non-coding RNA widely present in eukaryotes that play a central role in physiological and pathological conditions. Accumulating evidence has indicated that CircRNAs participated in modulating tumorigenesis by acting as a competing endogenous RNA (CeRNA). However, the roles and functions of CircRNAs in cellular senescence and aging of organisms remain largely obscure. We performed whole transcriptome sequencing to compare the expression patterns of circular RNAs in young and prematurely senescent human diploid fibroblast 2BS cells, and identified senescence-associated circRNAs (SAC-RNAs). Among these SAC-RNAs, we observed the significantly downregulated expression of CircRNAs originating from exons 6 and 7 circularization of the cyclin B1 gene (CCNB1), termed CircCCNB1. Reduced CircCCNB1 expression triggered senescence in young 2BS cells, as measured by increased senescence associated-beta-galactosidase (SA-β-gal) activity, enhanced expression of cyclin-dependent kinase inhibitor 1A (CDKN1A)/P21 and tumor protein 53 (TP53) expression, and reduced cell proliferation. Mechanistically, reduced CircCCNB1 level inhibited cyclin E2 (CCNE2) expression by modulating micro RNA (miR)-449a activity, which repressed cellular proliferation. Our data suggested that CircCCNB1may serve as a sponge against miR-449a to delay cellular senescence by targeting CCNE2. Targeting CircCCNB1 may represent a promising strategy for aging and age-related disease interventions. Furthermore, we also identified and characterized several kinds of the CircCCNB1-binding proteins (CBPs), which may contribute to the degradation of CircCCNB1

 

 

中文摘要

环状RNAcircRNAs)是一类新的非编码RNA,广泛存在于真核生物中,在生理和病理条件中起着重要作用。越来越多的证据表明circRNAs作为一种竞争性内源性RNAceRNA)参与了肿瘤发生的调控。然而,circRNAs在生物体细胞衰老和衰老过程中的作用和功能仍不清楚。我们对年轻和早衰的人二倍体成纤维细胞2BS细胞进行了全转录组测序,比较circRNAs的表达模式,并鉴定了衰老相关的circRNAsSAC-RNAs)。在这些SAC-RNAs中,我们观察到来源于cyclin B1基因(CCNB1)第6外显子和第7外显子循环的CircRNAs的显著下调表达,称为circcnb1。通过增加衰老相关β-半乳糖苷酶(SA-β-gal)活性、增加细胞周期蛋白依赖性激酶抑制剂1ACDKN1A/P21和肿瘤蛋白53TP53)的表达以及减少细胞增殖来测定,circcnb1的表达减少触发了年轻2BS细胞的衰老。在机制上,降低的CircCCNB1水平通过调节抑制细胞增殖的micro-RNAmiR-449a活性抑制细胞周期蛋白E2CCNE2)的表达。我们的数据表明,circcnb1可以作为miR-449a的海绵,通过靶向CCNE2来延缓细胞衰老。以circcnb1为靶点可能是一种有希望的老龄化和老年相关疾病干预策略。此外,我们还鉴定和鉴定了几种CircCCNB1结合蛋白(CBPs),它们可能有助于CircCCNB1的降解。

 

 

 

中文题目:系统鉴定circRNA及其调控网络揭示了它们在东方蜜蜂工蜂中肠中的潜在作用

英文题目:Chen D, Chen H, Du Y, Zhu Z, Wang J, Geng S, et al.Systematic identification of circular RNAs and corresponding regulatory networks unveil their potential roles in the midguts of eastern honeybee workers[J]. Appl Microbiol Biotechnol, 2019.

 

  名:Appl Microbiol Biotechnol   发表时间:2019.11   IF3.67

作者单位福建农林大学

测序项目:转录组测序

样品来源:蜜蜂

文章类型:研究型

 

英文摘要

Currently, knowledge of circular RNAs (circRNAs) in insects including honeybee is extremely limited. Here, differential expression profiles and regulatory networks of circRNAs in the midguts of Apiscerana cerana workers were comprehensively investigated using transcriptome sequencing and bioinformatics. In total, 9589 circRNAs (201-800 nt in length) were identified from 8-day-old and 11-day-old workers\' midguts (Ac1 and Ac2); among them, 5916 (61.70%) A. cerana cerana circRNAs showed conservation with our previously indentified circRNAs in Apis mellifera ligucstica workers\' midguts (Xiong et al., Acta Entomologica Sinica 61:1363-1375, 2018). Five circRNAs were confirmed by RT-PCR and Sanger sequencing. Interestingly, novel_circ_003723, novel_circ_002714, novel_circ_002451, and novel_circ_001980 were highly expressed in both Ac1 and Ac2. In addition, the source genes of circRNAs were involved in 34 GO terms including organelle and cellular process and 141 pathways such as endocytosis and Wnt signaling pathway. Moreover, 55 DEcircRNAs including 34 upregulated and 21 downregulated circRNAs were identified in Ac2 compared with Ac1. circRNA-miRNA regulatory networks indicated that 1060 circRNAs can target 74 miRNAs; additionally, the DEcircRNA-miRNA-mRNA networks suggested that 13 downregulated circRNAs can bind to eight miRNAs and 29 miRNA-targeted mRNAs, while 16 upregulated circRNAs can link to 9 miRNAs and 29 miRNA-targeted mRNAs. These results indicated that DEcircRNAs as ceRNAs may play a comprehensive role in the growth, development, and metabolism of the worker\'s midgut via regulating source genes and interacting with miRNAs. Notably, eight DEcircRNAs targeting miR-6001-y were likely to be key participants in the midgut development. Our findings not only offer a valuable resource for further studies on A. cerana cerana circRNA and novel insights into understanding the molecular mechanisms underlying the midgut development of eastern honeybee but also provide putative circRNA candidates for functional research in the near future and novel biomarkers for identification of eastern honeybee species including A. cerana cerana and honeybee diseases such as chalkbrood and microsporidiosis.

 

中文摘要

目前,包括蜜蜂在内的昆虫对circRNAs的认识极为有限。本文应用转录组测序和生物信息学方法,对中华蜜蜂(Apiscerana cerana)工蜂中肠circRNAs的差异表达谱和调控网络进行了研究。从8日龄和11日龄工人中肠(Ac1Ac2)共鉴定出9589circRNAs201-800 nt);其中,5916个(61.70%A.cerana cerana circRNAs与我们之前在意大利蜜蜂(Apis mellifera ligucstica)工人中肠鉴定出的circRNAs保持一致。RT-PCRSanger测序证实了5circRNA。有趣的是,在Ac1Ac2中都高度表达了novel_circ_003723novel_circ_002714novel_circ_002451novel_circ_001980。此外,circRNAs的源基因涉及细胞器和细胞过程等34GO和胞吞、Wnt信号途径等141条途径。此外,与Ac1相比,Ac2共鉴定出55差异表达circRNA,其中34个上调,21个下调。circRNA-miRNA调控网络表明,1060circRNA可以靶向74miRNA;此外,DEcircRNA-miRNA-mRNA网络表明,13个下调的circRNA可以与8miRNA29miRNA靶向的mRNA结合,而16个上调的circRNA可以与9miRNA29miRNA靶向的mRNA结合。这些结果表明,作为ceRNAsDEcircRNAs可能通过调节源基因和与miRNAs相互作用,在工人中肠的生长、发育和代谢中发挥综合作用。值得注意的是,8个靶向miR-6001-y的脱氧核糖核酸可能是中肠发育的关键参与者。我们的发现不仅为进一步研究中华蜜蜂中肠发育的分子机制提供了有价值的资源,而且为今后的功能研究和鉴定中华蜜蜂中肠发育的新生物标志物提供了可能的候选分子东方蜜蜂,包括中华蜜蜂和蜜蜂疾病,如白垩窝和小孢子虫病。

 

 

 

中文题目:全转录组RNA序列揭示了资阳香橙对铜毒性的mRNAslncRNAsmiRNAscircRNAs的全球分子反应和CRNA调控网络

英文题目:Fu XZ, Zhang XY, Qiu JY, et al. Whole-transcriptome RNA sequencing reveals the global molecular responses and ceRNA regulatory network of mRNAs, lncRNAs, miRNAs and circRNAs in response to copper toxicity in Ziyang Xiangcheng (Citrus junos Sieb. Ex Tanaka)[J]. BMC Plant Biol, 2019, 19(1):509.

 

  名:BMC Plant Biol        发表时间:2019.11       IF3.67

作者单位西南大学

样品来源:资阳香橙

文章类型:研究型

 

英文摘要

BACKGROUND: Copper (Cu) toxicity has become a potential threat for citrus production, but little is known about related mechanisms. This study aims to uncover the global landscape of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in response to Cu toxicity so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) and to provide valuable knowledge pertinent to Cu response in citrus.

RESULTS: Tolerance of four commonly used rootstocks to Cu toxicity was evaluated, and \'Ziyang Xiangcheng\' (Citrus junos) was found to be the most tolerant genotype. Then the roots and leaves sampled from \'Ziyang Xiangcheng\' with or without Cu treatment were used for whole-transcriptome sequencing. In total, 5734 and 222 mRNAs, 164 and 5 lncRNAs, 45 and 17 circRNAs, and 147 and 130 miRNAs were identified to be differentially expressed (DE) in Cu-treated roots and leaves, respectively, in comparison with the control. Gene ontology enrichment analysis showed that most of the DEmRNAs and targets of DElncRNAs and DEmiRNAs were annotated to the categories of \'oxidation-reduction\', \'phosphorylation\', \'membrane\', and \'ion binding\'. The ceRNA network was then constructed with the predicted pairs of DEmRNAs-DEmiRNAs and DElncRNAs-DEmiRNAs, which further revealed regulatory roles of these DERNAs in Cu toxicity.

CONCLUSIONS: A large number of mRNAs, lncRNAs, circRNAs, and miRNAs in \'Ziyang Xiangcheng\' were altered in response to Cu toxicity, which may play crucial roles in mitigation of Cu toxicity through the ceRNA regulatory network in this Cu-tolerant rootstock.

 

中文摘要:

背景:铜(Cu)的毒性已成为柑橘生产的潜在威胁,但相关机制知之甚少。本研究的目的是揭示全球的mRNAlncRNAscircRNAsmicroRNAmiRNA)响应Cu毒性,从而构建竞争性内源性RNAsceNAS)的调控网络,并提供有价值的知识与柑橘的Cu反应相关。

结果:对四种常用砧木对铜毒害的耐受性进行了评价,发现Ziyang Xiangcheng(柑橘属)是最耐基因型。然后对\'Ziyang Xiangcheng的根和叶进行全转录组测序。与对照相比,共鉴定出5734222mRNAs1645lncRNAs4517circRNAs以及147130miRNAsCu处理的根和叶中差异表达。基因本体富集分析表明,大多数的核蛋白体和DEmiRNAs的目标被注释到氧化还原磷酸化离子结合的范畴。然后用预测的DimRNNA DimRNsDelnCRNs DimiRNA构建CeRNA网络,进一步揭示这些DRNA在铜毒性中的调节作用。结论:在Cu毒性下,大量的Ziyang Xiangcheng基因、lncRNAscircRNAsmiRNAs发生了改变,这可能通过ceRNA调节网络在Cu抗性砧木中减轻Cu毒性起着关键作用。

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