Competing endogenous RNA network mediated by circ_3205 in SARS-CoV-2 infected cells.

Competing endogenous RNA network mediated by circ_3205 in SARS-CoV-2 infected cells.
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DOI:
10.1007/s00018-021-04119-8
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发表时间:
2022-01-17
期刊:
Cellular and molecular life sciences : CMLS
影响因子:
--
通讯作者:
Purrello M
Purrello M
中科院分区:
其他
文献类型:
--
作者:
Barbagallo D;Palermo CI;Barbagallo C;Battaglia R;Caponnetto A;Spina V;Ragusa M;Di Pietro C;Scalia G;Purrello M

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严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)是贝塔冠状病毒科的新成员,导致最近爆发的新冠肺炎大流行。为了开始探索宿主细胞感染后的分子事件,我们查询了VirusCircBase,并鉴定了一个预测由SARS-CoV-2,CIRC_3205合成的环状RNA(CircRNA),我们使用它来探测:(I)由三个SARS-CoV-2感染(阳性)或未感染(UCs)个体的鼻咽拭子中的两个细胞池组成的训练队列;(Ii)由12个阳性样本和3个阴性样本组成的验证队列。实时荧光定量聚合酶链式反应检测CircRNAs、miRNAs和miRNA靶基因的表达。用TarpMiR、环状RNA共同靶标分析(ACT)和STarMir工具预测CircRNA-miRNA相互作用。从Diana miRPath v3.0检索到生物过程的浓缩和预测的miRNA靶点列表。结果表明,预测的SARS-CoV-2CIRC_3205基因仅在阳性样本中表达,其量与SARS-CoV-2尖峰蛋白(S)和病毒载量呈正相关(r值分别为 = 0.80952和0.84867,Spearman相关检验)。所有三种预测工具都预测人(Hsa)miR-298与CIRC_3205相互作用。KCNMB4和PRKCE被预测为hSA-miR-298靶点。有趣的是,两者的功能与凝血和免疫反应有关。KCNMB4和PRKCEmRNAs在阳性标本中表达上调,分别是UC的6倍和8.1倍(p值分别为 = 0.049和0.02,t检验),并与CIRC3205的表达呈正相关(r值分别为 = 0.6和0.2 5,Spearman相关检验)。我们的结果令人信服地表明,CIRC_3205是SARS-CoV-2感染宿主细胞后合成的CircRNA,它可能是一个竞争性内源RNA(CerNA),吞噬hsa-miR-298,促进KCNMB4和PRKCE mRNAs的上调。网上版载有补充材料,可在10.1007/s00018-021-04119-8查阅。
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new member of the Betacoronaviridae family, responsible for the recent pandemic outbreak of COVID-19. To start exploring the molecular events that follow host cell infection, we queried VirusCircBase and identified a circular RNA (circRNA) predicted to be synthesized by SARS-CoV-2, circ_3205, which we used to probe: (i) a training cohort comprised of two pools of cells from three nasopharyngeal swabs of SARS-CoV-2 infected (positive) or uninfected (negative, UCs) individuals; (ii) a validation cohort made up of 12 positive and 3 negative samples. The expression of circRNAs, miRNAs and miRNA targets was assayed through real-time PCR. CircRNA–miRNA interactions were predicted by TarpMiR, Analysis of Common Targets for circular RNAs (ACT), and STarMir tools. Enrichment of the biological processes and the list of predicted miRNA targets were retrieved from DIANA miRPath v3.0. Our results showed that the predicted SARS-CoV-2 circ_3205 was expressed only in positive samples and its amount positively correlated with that of SARS-CoV-2 Spike (S) mRNA and the viral load (r values = 0.80952 and 0.84867, Spearman’s correlation test, respectively). Human (hsa) miR-298 was predicted to interact with circ_3205 by all three predictive tools. KCNMB4 and PRKCE were predicted as hsa-miR-298 targets. Interestingly, the function of both is correlated with blood coagulation and immune response. KCNMB4 and PRKCE mRNAs were upregulated in positive samples as compared to UCs (6 and 8.1-fold, p values = 0.049 and 0.02, Student’s t test, respectively) and their expression positively correlated with that of circ_3205 (r values = 0.6 and 0.25, Spearman’s correlation test, respectively). We propose that our results convincingly suggest that circ_3205 is a circRNA synthesized by SARS-CoV-2 upon host cell infection and that it may behave as a competitive endogenous RNA (ceRNA), sponging hsa-miR-298 and contributing to the upregulation of KCNMB4 and PRKCE mRNAs. The online version contains supplementary material available at 10.1007/s00018-021-04119-8.
DOI: 10.1038/s41380-019-0610-2
发表时间: 2021-10
影响因子: 11
作者:
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发表时间: 2021-03-01
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影响因子: 4.8
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DOI: 10.1095/biolreprod.116.142711
发表时间: 2016-12-01
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