Immunomodulatory LncRNA on antisense strand of ICAM-1 augments SARS-CoV-2 infection-associated airway mucoinflammatory phenotype.
Immunomodulatory LncRNA on antisense strand of ICAM-1 augments SARS-CoV-2 infection-associated airway mucoinflammatory phenotype.
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DOI：
10.1016/j.isci.2022.104685
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发表时间：
2022-08-19
期刊：
影响因子：
5.8
通讯作者：
Chand, Hitendra S.
中科院分区：
文献类型：
--
作者：
Devadoss, Dinesh;Acharya, Arpan;Manevski, Marko;Houserova, Dominika;Cioffi, Michael D.;Pandey, Kabita;Nair, Madhavan;Chapagain, Prem;Mirsaeidi, Mehdi;Borchert, Glen M.;Byrareddy, Siddappa N.;Chand, Hitendra S.
非编码RNA是粘膜炎症反应的重要调节因子，但对气道长链非编码RNA（lncRNA）在COVID-19中的作用知之甚少。RNA-seq分析显示，与未感染的对照组相比，COVID-19患者鼻样本中IL-6、ICAM-1、CXCL-8和SCGB 1A 1炎症因子; MUC 5AC和MUC 5 B粘蛋白;以及SPDEF、FOXA 3和FOXJ 1转录因子的表达增加了4倍以上。ICAM-1或LASI反义链上的lncRNA在COVID-19患者中诱导2倍，其表达与病毒载量直接相关。SARS-CoV-2感染的3D气道模型在很大程度上概括了这些临床发现。RNA显微镜和分子模拟表明病毒RNA和LASI lncRNA之间可能存在相互作用。值得注意的是，阻断LASIlncRNA减少了SARS-CoV-2复制并抑制了MUC 5AC粘蛋白水平和相关炎症，并且选择了LASI-dependent miRNA（例如，let-7b-5p和miR-200a-5p）。因此，LASI lncRNA代表SARS-CoV-2感染和相关气道粘膜炎症反应的重要促进剂。COVID 19气道粘膜炎症反应与LASI lncRNA水平密切相关LASI lncRNA沉默抑制SARS-CoV-2病毒载量和相关炎症LASI lncRNA显示与SARS-CoV-2刺突病毒RNA的潜在直接相互作用LASI调节气道上皮miRNA的表达以调节炎症分子生物学;基因调控的分子机制;免疫学;病毒学
Noncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression of IL-6, ICAM-1, CXCL-8, and SCGB1A1 inflammatory factors; MUC5AC and MUC5B mucins; and SPDEF, FOXA3, and FOXJ1 transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 or LASI was induced 2-fold in COVID-19 patients, and its expression was directly correlated with viral loads. A SARS-CoV-2-infected 3D-airway model largely recapitulated these clinical findings. RNA microscopy and molecular modeling indicated a possible interaction between viral RNA and LASI lncRNA. Notably, blocking LASI lncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and select LASI-dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus, LASI lncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response. COVID19 airway mucoinflammatory response strongly correlates with LASI lncRNA level Silencing LASI lncRNA suppresses SARS-CoV-2 viral load and associated inflammation LASI lncRNA shows a potential direct interaction with SARS-CoV-2 spike viral RNA Hosts of airway epithelial miRNAs are modulated by LASI to regulate inflammation Molecular biology; Molecular mechanism of gene regulation; Immunology; Virology
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影响因子：
6.7
作者：
Fageeh H;Alshehri A;Fageeh H;Bizzoca ME;Lo Muzio L;Quadri MFA
通讯作者：
Quadri MFA
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
5.7
作者：
Devadoss D;Singh SP;Acharya A;Do KC;Periyasamy P;Manevski M;Mishra N;Tellez CS;Ramakrishnan S;Belinsky SA;Byrareddy SN;Buch S;Chand HS;Sopori M
通讯作者：
Sopori M
DOI：
10.1002/cjp2.224
发表时间：
2021-09
期刊：
The journal of pathology. Clinical research
影响因子：
--
作者：
Fließer E;Birnhuber A;Marsh LM;Gschwandtner E;Klepetko W;Olschewski H;Kwapiszewska G
通讯作者：
Kwapiszewska G
影响因子：
3.5
作者：
Chow JT;Salmena L
通讯作者：
Salmena L