scholarly journals Long Noncoding RNA NTT Context-Dependently Regulates MYB by Interacting With Activated Complex in Hepatocellular Carcinoma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Ya-Sian Chang ◽  
Ya-Ting Lee ◽  
Ju-Chen Yen ◽  
Yuli C. Chang ◽  
Li-Li Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Cellular Migration ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Colon Cancers ◽  
Activated Complex

BackgroundLong noncoding RNA (lncRNA) mediates the pathogenesis of various diseases, including cancer and cardiovascular, infectious, and metabolic diseases. This study examined the role of lncRNA NTT in the development and progression of cancer.MethodsThe expression of NTT was determined using tissues containing complementary DNA (cDNA) from patients with liver, lung, kidney, oral, and colon cancers. The expression of cis-acting genes adjacent to the NTT locus (CTGF, STX7, MYB, BCLAF1, IFNGR1, TNFAIP3, and HIVEP2) was also assessed. We used knockdown and chromatin immunoprecipitation (ChIP) assays to identify the cis-acting genes that interact with NTT.ResultsNTT was most significantly downregulated in hepatocellular carcinoma (HCC), while a higher NTT level correlated with a shorter survival time of patients with HCC. Multivariate analysis indicated NTT was not an independent predictor for overall survival. MYB was significantly upregulated, and its increased expression was associated with dismal survival in HCC patients, similar to the results for NTT. NTT knockdown significantly decreased cellular migration. ChIP of HCC cell lines revealed that NTT is regulated by the transcription factor ATF3 and binds to the MYB promoter via the activated complex. Additionally, when NTT was knocked down, the expression of MYB target genes such as Bcl-xL, cyclinD1, and VEGF was also downregulated. NTT could play a positive or negative regulator for MYB with a context-dependent manner in both HCC tissues and animal model.ConclusionOur study suggests that NTT plays a key role in HCC progression via MYB-regulated target genes and may serve as a novel therapeutic target.

scholarly journals NF-κB-Interacting Long Noncoding RNA Regulates HIV-1 Replication and Latency by Repressing NF-κB Signaling

2020 ◽  
Vol 94 (17) ◽  
Author(s):  
Hong Wang ◽  
Yue Liu ◽  
Chen Huan ◽  
Jing Yang ◽  
Zhaolong Li ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Long Noncoding Rna ◽  
Transcription Initiation ◽  
Noncoding Rna ◽  
Ectopic Expression ◽  
Terminal Repeat ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Iκb Kinase ◽  
Hiv 1

ABSTRACT NF-κB-interacting long noncoding RNA (NKILA) was recently identified as a negative regulator of NF-κB signaling and plays an important role in the development of various cancers. It is well known that NF-κB-mediated activation of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-driven gene expression is required for HIV-1 transcription and reactivation of latency. However, whether NKILA plays essential roles in HIV-1 replication and latency is unclear. Here, by ectopic expression and silencing experiments, we demonstrate that NKILA potently inhibits HIV-1 replication in an NF-κB-dependent manner by suppressing HIV-1 LTR promoter activity. Moreover, NKILA showed broad-spectrum inhibition on the replication of HIV-1 clones with different coreceptor tropisms as well as on LTR activity of various HIV-1 clinical subtypes. Chromatin immunoprecipitation (ChIP) assays revealed that NKILA expression abolishes the recruitment of p65 to the duplicated κB binding sites in the HIV-1 LTR. NKILA mutants disrupting NF-κB inhibition also lost the ability to inhibit HIV-1 replication. Notably, HIV-1 infection or reactivation significantly downregulated NKILA expression in T cells in order to facilitate viral replication. Downregulated NKILA was mainly due to reduced acetylation of histone K27 on the promoter of NKILA by HIV-1 infection, which blocks NKILA expression. Knockdown of NKILA promoted the reactivation of latent HIV-1 upon phorbol myristate acetate (PMA) stimulation, while ectopic NKILA suppressed the reactivation in a well-established clinical model of withdrawal of azidothymidine (AZT) in vitro. These findings improve our understanding of the functional suppression of HIV-1 replication and latency by NKILA through NF-κB signaling. IMPORTANCE The NF-κB pathway plays key roles in HIV-1 replication and reactivation of HIV-1 latency. A regulator inhibiting NF-κB activation may be a promising therapeutic strategy against HIV-1. Recently, NF-κB-interacting long noncoding RNA (NKILA) was identified to suppress the development of different human cancers by inhibiting IκB kinase (IKK)-induced IκB phosphorylation and NF-κB pathway activation, whereas the relationship between NKILA and HIV-1 replication is still unknown. Here, our results show that NKILA inhibits HIV-1 replication and reactivation by suppressing HIV-1 long terminal repeat (LTR)-driven transcription initiation. Moreover, NKILA inhibited the replication of HIV-1 clones with different coreceptor tropisms. This project may reveal a target for the development of novel anti-HIV drugs.

scholarly journals The long noncoding RNA TUG1 acts as a competing endogenous RNA to regulate the Hedgehog pathway by targeting miR-132 in hepatocellular carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (39) ◽  
pp. 65932-65945 ◽  
Author(s):  
Jingjing Li ◽  
Qinghui Zhang ◽  
Xiaoming Fan ◽  
Wenhui Mo ◽  
Weiqi Dai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Hedgehog Pathway ◽  
Competing Endogenous Rna

scholarly journals Super-Enhancer–Associated Long Noncoding RNA HCCL5 Is Activated by ZEB1 and Promotes the Malignancy of Hepatocellular Carcinoma

2018 ◽  
Vol 79 (3) ◽  
pp. 572-584 ◽  
Author(s):  
Li Peng ◽  
Binyuan Jiang ◽  
Xiaoqing Yuan ◽  
Yuntan Qiu ◽  
Jiangyun Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Super Enhancer

scholarly journals GW29-e1174 The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy

2018 ◽  
Vol 72 (16) ◽  
pp. C36
Author(s):  
Lantao Liu ◽  
Yao Song ◽  
Linling Li ◽  
Song Zuo ◽  
Nian Liu ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Negative Regulator ◽  
Cardiomyocyte Hypertrophy

scholarly journals A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock

2021 ◽  
Vol 118 (7) ◽  
pp. e2016648118
Author(s):  
Apple Cortez Vollmers ◽  
Sergio Covarrubias ◽  
Daisy Kuang ◽  
Aaron Shulkin ◽  
Justin Iwuagwu ◽  
...  
Keyword(s):  
Immune Response ◽  
Knockout Mice ◽  
Noncoding Rna ◽  
Target Genes ◽  
Blood Clot ◽  
Multiorgan Failure ◽  
Endotoxic Shock ◽  
Negative Regulator ◽  
Inflammatory Genes ◽  
Lps Challenge

Recent studies have identified thousands of long noncoding RNAs (lncRNAs) in mammalian genomes that regulate gene expression in different biological processes. Although lncRNAs have been identified in a variety of immune cells and implicated in immune response, the biological function and mechanism of the majority remain unexplored, especially in sepsis. Here, we identify a role for a lncRNA—gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC)—previously characterized for its role in cancer, now in the context of innate immunity, macrophages, and LPS-induced endotoxic shock. Transcriptome analysis of macrophages from humans and mice reveals that GAPLINC is a conserved lncRNA that is highly expressed following macrophage differentiation. Upon inflammatory activation, GAPLINC is rapidly down-regulated. Macrophages depleted of GAPLINC display enhanced expression of inflammatory genes at baseline, while overexpression of GAPLINC suppresses this response. Consistent with GAPLINC-depleted cells, Gaplinc knockout mice display enhanced basal levels of inflammatory genes and show resistance to LPS-induced endotoxic shock. Mechanistically, survival is linked to increased levels of nuclear NF-κB in Gaplinc knockout mice that drives basal expression of target genes typically only activated following inflammatory stimulation. We show that this activation of immune response genes prior to LPS challenge leads to decreased blood clot formation, which protects Gaplinc knockout mice from multiorgan failure and death. Together, our results identify a previously unknown function for GAPLINC as a negative regulator of inflammation and uncover a key role for this lncRNA in modulating endotoxic shock.

scholarly journals An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Dengliang Lei ◽  
Yue Chen ◽  
Yang Zhou ◽  
Gangli Hu ◽  
Fang Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Roc Curves ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Highly Correlated

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA (lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of patients with liver cancer, but its mechanism of action must be further elucidated by experiments.

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