Hepatitis B Virus–Upregulated LNC‐HUR1 Promotes Cell Proliferation and Tumorigenesis by Blocking p53 Activity

Liu, Ningning; Liu, Qi; Yang, Xiaohai; Zhang, Fang; Li, Xinda; Ma, Yuanwu; Guan, Feifei; Zhao, Xin; Li, Zhiwei; Zhang, Lianfeng; Ye, Xin

doi:10.1002/hep.30098

Cited by 51 publications

(44 citation statements)

References 32 publications

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“…RNA immunoprecipitation. A549 lnc-MxA-overexpressing cells were seeded and infected with SeV at a multiplicity of infection (MOI) of 1 for 12 h. Then, the cells were cross-linked by UV, as previously described (45). The cells were washed with phosphate-buffered saline (PBS) and lysed with 1 ml radioimmunoprecipitation assay (RIPA) buffer containing protease inhibitor (Roche, Switzerland) and RNase inhibitor (Thermo, USA).…”

Section: Methodsmentioning

confidence: 99%

Long Noncoding RNA Lnc-MxA Inhibits Beta Interferon Transcription by Forming RNA-DNA Triplexes at Its Promoter

Guo

et al. 2019

J Virol

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Previously, we identified a set of long noncoding RNAs (lncRNAs) that were differentially expressed in influenza A virus (IAV)-infected cells. In this study, we focused on lnc-MxA, which is upregulated during IAV infection. We found that the overexpression of lnc-MxA facilitates the replication of IAV, while the knockdown of lnc-MxA inhibits viral replication. Further studies demonstrated that lnc-MxA is an interferon-stimulated gene. However, lnc-MxA inhibits the Sendai virus (SeV)- and IAV-induced activation of beta interferon (IFN-β). A luciferase assay indicated that lnc-MxA inhibits the activation of the IFN-β reporter upon stimulation with RIG-I, MAVS, TBK1, or active IRF3 (IRF3-5D). These data indicated that lnc-MxA negatively regulates the RIG-I-mediated antiviral immune response. A chromatin immunoprecipitation (ChIP) assay showed that the enrichment of IRF3 and p65 at the IFN-β promoter in lnc-MxA-overexpressing cells was significantly lower than that in control cells, indicating that lnc-MxA interfered with the binding of IRF3 and p65 to the IFN-β promoter. Chromatin isolation by RNA purification (ChIRP), triplex pulldown, and biolayer interferometry assays indicated that lnc-MxA can bind to the IFN-β promoter. Furthermore, an electrophoretic mobility shift assay (EMSA) showed that lnc-MxA can form complexes with the IFN-β promoter fragment. These results demonstrated that lnc-MxA can form a triplex with the IFN-β promoter to interfere with the activation of IFN-β transcription. Using a vesicular stomatitis virus (VSV) infection assay, we confirmed that lnc-MxA can repress the RIG-I-like receptor (RLR)-mediated antiviral immune response and influence the antiviral status of cells. In conclusion, we revealed that lnc-MxA is an interferon-stimulated gene (ISG) that negatively regulates the transcription of IFN-β by forming an RNA-DNA triplex. IMPORTANCE IAV can be recognized as a nonself molecular pattern by host immune systems and can cause immune responses. However, the intense immune response induced by influenza virus, known as a “cytokine storm,” can also cause widespread tissue damage (X. Z. J. Guo and P. G. Thomas, Semin Immunopathol 39:541–550, 2017, https://doi.org/10.1007/s00281-017-0636-y; S. Yokota, Nihon Rinsho 61:1953–1958, 2003; I. A. Clark, Immunol Cell Biol 85:271–273, 2007). Meanwhile, the detailed mechanisms involved in the balancing of immune responses in host cells are not well understood. Our studies reveal that, as an IFN-inducible gene, lnc-MxA functions as a negative regulator of the antiviral immune response. We uncovered the mechanism by which lnc-MxA inhibits the activation of IFN-β transcription. Our findings demonstrate that, as an ISG, lnc-MxA plays an important role in the negative-feedback loop involved in maintaining immune homeostasis.

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Section: Methodsmentioning

confidence: 99%

Long Noncoding RNA Lnc-MxA Inhibits Beta Interferon Transcription by Forming RNA-DNA Triplexes at Its Promoter

Guo

et al. 2019

J Virol

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“…Hepatitis viruses hijack host cells to facilitate their replication or production via multiple mechanisms, one of which is regulating the transcription of certain lncRNAs. For instance, the HBV X protein (HBx) upregulates oncogenic lncRNA HUR1, which binds and blocks p53 to promote HCC growth [23]. Besides, HBx can also downregulate tumor suppressive lncRNA Dreh, leading to re-expression of vimentin and promoting HCC metastasis [24].…”

Section: Viral Infectionmentioning

confidence: 99%

The role of long noncoding RNAs in hepatocellular carcinoma

et al. 2020

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Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms underlying HCC pathogenesis have not been fully understood. Emerging evidences have recently suggested the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of HCC. Various HCC-related lncRNAs have been shown to possess aberrant expression and participate in cancerous phenotypes (e.g. persistent proliferation, evading apoptosis, accelerated vessel formation and gain of invasive capability) through their binding with DNA, RNA or proteins, or encoding small peptides. Thus, a deeper understanding of lncRNA dysregulation would provide new insights into HCC pathogenesis and novel tools for the early diagnosis and treatment of HCC. In this review, we summarize the dysregulation of lncRNAs expression in HCC and their tumor suppressive or oncogenic roles during HCC tumorigenesis. Moreover, we discuss the diagnostic and therapeutic potentials of lncRNAs in HCC.

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“…Transfection efficiency of PITPNA-AS1 overexpression or knockdown was also determined using Northern blot as previously elucidated 37 .…”

Section: Northern Blotmentioning

confidence: 99%

PITPNA-AS1 abrogates the inhibition of miR-876-5p on WNT5A to facilitate hepatocellular carcinoma progression

Sun

Zhang

et al. 2019

Cell Death Dis

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LncRNA PITPNA-AS1 was a newly identified lncRNA which has never been studied in cancers. Whether PITPNA-AS1 participated in the development of hepatocellular carcinoma (HCC) is obscure. Given the coaction of lncRNAs and miRNAs to carcinogenesis, the purpose of the present research is to inquire how PITPNA-AS1 affects HCC progression. Firstly, PITPNA-AS1 was observed to be heightened in HCC tissues. Then function assays proved that overexpressing or silencing PITPNA-AS1 could manipulate the proliferation and motility of HCC cells. Besides, PITPNA-AS1 was located in the cytoplasm. Among the candidate miRNAs of PITPNA-AS1, miR-876-5p was an obvious target. Moreover, mechanism experiments validated that PITPNA-AS1 modulated WNT5A expression by targeting miR-876-5p. Rescue experiments affirmed that WNT5A silencing rescued the miR-876-5p suppression-induced cellular processes in PITPNA-AS1-silenced Hep3B cells. And in vivo experiments determined that PITPNA-AS1 regulated HCC progression in vivo via miR-876-5p/WNT5A pathway. In conclusion, this work shed lights on the modulatory mechanism of PITPNA-AS1/miR-876-5p/WNT5A axis in HCC, which might be pivotal for exploring effective diagnostic biomarkers and treatment strategies for HCC patients.

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Hepatitis B Virus–Upregulated LNC‐HUR1 Promotes Cell Proliferation and Tumorigenesis by Blocking p53 Activity

Cited by 51 publications

References 32 publications

Long Noncoding RNA Lnc-MxA Inhibits Beta Interferon Transcription by Forming RNA-DNA Triplexes at Its Promoter

Long Noncoding RNA Lnc-MxA Inhibits Beta Interferon Transcription by Forming RNA-DNA Triplexes at Its Promoter

The role of long noncoding RNAs in hepatocellular carcinoma

PITPNA-AS1 abrogates the inhibition of miR-876-5p on WNT5A to facilitate hepatocellular carcinoma progression

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