Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter

Qu, Di; Sun, Wei‐Zen; Li, Li; Ma, Li; Sun, Li; Jin, Xia; Li, Taisheng; Hou, Wei; Wang, Jianhua

doi:10.1093/nar/gkz117

Cited by 127 publications

(118 citation statements)

References 83 publications

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“…58 By associating with PRC2, MALAT1 detaches EZH2 bound to the HIV-1 LTR promoter, leading to the removal of H3K27me3 and reversal of epigenetic silencing of HIV-1 transcription. 59 lncRNAs from the antisense strand of p21 gene inhibit the transcription of p21 by inducing H3K27 methylation in its promoter region. 60 It has also been reported that altered expression of miRNAs and methylation of their promoters were correlated in neuroblastoma.…”

Section: Discussionmentioning

confidence: 99%

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

Zhang

Ruan

et al. 2020

Molecular Therapy

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Studies have found that RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are dysregulated and play an important regulatory role in the development of tumors. Based on The Cancer Genome Atlas (TCGA) database, our findings from experiments, and the evidence of previous studies, we screened DiGeorge syndrome critical region gene 8 (DGCR8), ZFAT antisense RNA 1 (ZFAT-AS1), and caudal type homeobox 2 (CDX2) as research candidates. In the present study, DGCR8 and CDX2 were highly expressed and ZFAT-AS1 was markedly downregulated in glioma tissues and cells. DGCR8 or CDX2 knockdown or ZFAT-AS1 overexpression suppressed glioma cell proliferation, migration, and invasion and facilitated apoptosis. DGCR8 might decrease ZFAT-AS1 expression by attenuating its stability in a manner of inducing its cleavage. Importantly, ZFAT-AS1 could inhibit CDX2 transcription by mediating the methylation of histone H3 on lysine 27 (H3K27me3) modification induced by PRC2 in the CDX2 promoter region. In addition, CDX2 transcriptionally activated DGCR8 expression by binding to its promoter regions, forming a positive feedback loop of DGCR8/ZFAT-AS1/ CDX2. In conclusion, DGCR8/ZFAT-AS1 promotes CDX2 transcription in a PRC2 complex-dependent manner to facilitate the malignant biological behavior of glioma cells.

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Section: Discussionmentioning

confidence: 99%

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

Zhang

Ruan

et al. 2020

Molecular Therapy

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“…However, splicing alterations were not found after MALAT1 ablation in mice [37]. In contrast, alternative functions for MALAT1 were recently identified: MALAT1 could interact with the demethylated form of Chromobox homolog 4 (CBX4), also referred to as Polycomb 2 (Pc2), a component of the Polycomb Repressive Complex 1 (PRC1) [35,39,40]. This interaction controls the re-localization of growth control genes.…”

Section: Discussionmentioning

confidence: 99%

Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma

Liang

et al. 2019

Eur Arch Otorhinolaryngol

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Purpose The long non-coding RNA MALAT1 is a predictive marker in several solid tumors with highly conserved sequences. However, the role of non-coding RNA in development of laryngeal or hypopharyngeal cancer remains unclear. Methods Tumor tissues and adjacent non-cancer tissues of 24 patients were collected. We detected the expression of MALAT1 in laryngeal cancer tissues and hypopharyngeal cancer tissues. Moreover, we developed a MALAT1 silencing model in human laryngeal tumor cells by transfecting MALAT1 small interfering RNA into human laryngeal carcinoma cell line Hep-2 and pharyngeal carcinoma cell line FaDu with Lipofectamine 2000 system. Cell cycle analysis, Cell Counting Kit-8 assay, Transwell assay, quantitative reverse transcription PCR, and wound-healing assays were performed to evaluate the impact of MALAT1 depletion on laryngeal or hypopharyngeal cancer cell's growth, proliferation, apoptosis, invasion and migration. Results MALAT1 was significantly up-regulated in laryngeal and hypopharyngeal carcinoma cells. MALAT1 down-regulation induced the increased apoptosis of both cell lines and suppressed cells' proliferation. Cells were arrested in G1/G2 phase and cells of S phase were significantly decreased. Down-regulation of MALAT1 expression can also inhibit the migration and invasion of laryngeal squamous cell carcinoma cell (Hep-2) and hypopharyngeal cancer cell (FaDu). Conclusion In summary, our deactivation model of MALAT1 disentangled the active function of it as a regulator of gene expression governing the hallmarks of laryngeal and hypopharyngeal cancer. Blocking this long non-coding RNA may restrain the development of laryngeal cancer.

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“…The knockdown of lncRNA NRON enhanced HIV-1 replication through increased activity of nuclear factor of activated T-cells (NFAT) and the viral long terminal repeat (LTR) [14]. Similarly, lncRNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter [15].…”

Section: Studying the Characteristics Of The Autoimmune Factors Of Ecmentioning

confidence: 99%

Peer Review #1 of "RNA sequencing of CD4 T-cells reveals the relationships between lncRNA-mRNA co-expression in elite controller vs. HIV-positive infected patients (v0.1)"

2020

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Background: Elite controller refers to a patient with human immunodeficiency virus infection with an undetected viral load in the absence of highly active antiretroviral therapy. Studies on gene expression and regulation in these individuals are limited but significant, and have helped researchers and clinicians to understand the interrelationships between HIV and its host. Methods: We collected CD4 T-cell samples from two elite controllers (ECs), two HIV-positive infected patients (HPs), and two healthy controls (HCs) to perform second-generation transcriptome sequencing. Using the Cufflinks software, we calculated the Fragments Per Kilobase of transcript per Million fragments mapped (FPKM) and identified differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs), with corrected P value < 0.05 (based on a false discovery rate (FDR) < 0.05). We then constructed a protein-protein interaction network using cytoHubba and a long non-coding RNA-mRNA co-expression network based on the Pearson correlation coefficient. Results: In total, 1109 linear correlations of DE lncRNAs targeting DE mRNAs were found and several interesting interactions were identified as being associated with viral infections and immune responses within the networks based on these correlations. Among these lncRNA-mRNA relationships, hub mRNAs including HDAC6, MAPK8, MAPK9, ATM and their corresponding annotated co-expressed lncRNAs presented strong correlations with the MAPK-NF-kappa B pathway, which plays a role in the reactivation and replication of the virus. Conclusions: Using RNA-sequencing, we systematically analyzed the expression profiles of lncRNAs and mRNAs from CD4+ T cells from ECs, HPs, and HCs, and constructed a co-expression network based on the relationships among DE transcripts and database annotations. This was the first study to examine gene transcription in elite controllers and to study their functional relationships. Our results provide a reference for subsequent functional verification at the molecular or cellular level.

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Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter

Cited by 127 publications

References 83 publications

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma

Peer Review #1 of "RNA sequencing of CD4 T-cells reveals the relationships between lncRNA-mRNA co-expression in elite controller vs. HIV-positive infected patients (v0.1)"

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