The bromodomain inhibitor JQ1 up-regulates the long non-coding RNA MALAT1 in cultured human hepatic carcinoma cells

Choi, Hae In; An, Ga Yeong; Yoo, Eunyoung; Baek, Mina; Binas, Bert; Chai, Jin Choul; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

doi:10.1038/s41598-022-11868-4

Cited by 7 publications

(6 citation statements)

References 55 publications

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“…Our differential expression analysis of genes had identified 193 differentially expressed lncRNAs, of which 162 genes were identified as SE-lncRNAs and 15 SE-lncRNAs were differentially expressed. In line with our finding, a plethora of evidence supports that JQ1 can alter the expression profile of lncRNAs in cancer cells and exert a critical role in the proliferation inhibition of cancers ( Baek et al, 2022 ; Choi et al, 2022 ; Liu et al, 2021 ). The general consensus is that lncRNAs exert physiological regulatory effects by regulating mRNAs.…”

Section: Discussionsupporting

confidence: 91%

Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells

Zheng,

Huang,

Xiao

et al. 2024

PeerJ

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Objective To investigate the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related lncRNAs (SE-lncRNAs) and mRNAs in cervical cancer (CC) HeLa-cells. Methods The CCK8 method was implemented to detect the inhibitory effect of JQ1 on HeLa cells and explore the best inhibitory concentration. Whole transcriptome sequencing was performed to detect the changes of lncRNAs and mRNAs expression profiles in cells of the JQ1 treatment group and control group, respectively. The differentially expressed SE-lncRNAs were obtained by matching, while the co-expressed mRNAs were obtained by Pearson correlation analysis. Results The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time (P < 0.05). Under the experimental conditions of three concentrations of 0.01, 0.1 and 1 μmol/L of JQ1 on HeLa cells at 24, 48, 72 and 120 h, 1 μmol/L of JQ1 at 72 and 120 h had the same cell viability and the strongest cell proliferation inhibition. In order to understand the inhibitory mechanism of JQ1 on HeLa cells, this study analyzed the expression profile differences from the perspective of SE-lncRNAs and mRNAs. A total of 162 SE-lncRNAs were identified, of which 8 SE-lncRNAs were down-regulated and seven SE-lncRNAs were up-regulated. A total of 418 differentially expressed mRNAs related to SE-lncRNAs were identified, of which 395 mRNAs had positive correlation with 12 SE-lncRNAs and 408 mRNAs had negative correlation with 15 SE-lncRNAs. Conclusion JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.

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Section: Discussionsupporting

confidence: 91%

Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells

Zheng,

Huang,

Xiao

et al. 2024

PeerJ

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“…Previous studies demonstrated that JQ1, a small molecule, can specifically dislodge BRD4 from enhancers, thereby dissolving mediator and RNAPII clusters ( 50 , 51 ). Treatment with JQ1 can cause reconfiguration of chromatin structure in selected gene loci ( 52 ). We observed a significantly diminished ligation efficiency in the same region following JQ1 treatment, indicating that the interaction observed between the transcription start site region of AKR1C1 and the distal G4 is P–E interaction.…”

Section: Resultsmentioning

confidence: 99%

G-quadruplex DNA contributes to RNA polymerase II-mediated 3D chromatin architecture

Yuan

Wang

2023

Nucleic Acids Research

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High-order chromatin organization plays an important role in biological processes and disease development. Previous studies revealed a widespread occurrence of guanine quadruplex (G4) structures in the human genome, with enrichment in gene regulatory regions, especially in promoters. However, it remains unclear whether G4 structures contribute to RNA polymerase II (RNAPII)-mediated long-range DNA interactions and transcription activity. In this study, we conducted an intuitive overlapping analysis of previously published RNAPII ChIA-PET (chromatin interaction analysis with paired-end tag) and BG4 ChIP-seq (chromatin immunoprecipitation followed by sequencing using a G4 structure-specific antibody) data. We observed a strong positive correlation between RNAPII-linked DNA loops and G4 structures in chromatin. Additionally, our RNAPII HiChIP-seq (in situ Hi-C followed by ChIP-seq) results showed that treatment of HepG2 cells with pyridostatin (PDS), a small-molecule G4-binding ligand, could diminish RNAPII-linked long-range DNA contacts, with more pronounced diminutions being observed for those contacts involving G4 structure loci. RNA sequencing data revealed that PDS treatment modulates the expression of not only genes with G4 structures in their promoters, but also those with promoters being connected with distal G4s through RNAPII-linked long-range DNA interactions. Together, our data substantiate the function of DNA G4s in RNAPII-associated DNA looping and transcription regulation.

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“…For this study, we used the RNA-seq data of our previous paper (GSE155408). To identify DElncRNAs, a comprehensive reference list of known lncRNAs was included in the processing of the RNA-seq data [ 10 , 35 , 36 ]. Briefly, FASTQ data were quality controlled and trimmed with Trimmomatic (version 0.36) [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

Analysis of differentially expressed long non-coding RNAs in LPS-induced human HMC3 microglial cells

et al. 2022

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Background Long non-coding RNAs (lncRNAs) are emerging as key modulators of inflammatory gene expression, but their roles in neuroinflammation are poorly understood. Here, we identified the inflammation-related lncRNAs and correlated mRNAs of the lipopolysaccharide (LPS)-treated human microglial cell line HMC3. We explored their potential roles and interactions using bioinformatics tools such as gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), and weighted gene co-expression network analysis (WGCNA). Results We identified 5 differentially expressed (DE) lncRNAs, 4 of which (AC083837.1, IRF1-AS1, LINC02605, and MIR3142HG) are novel for microglia. The DElncRNAs with their correlated DEmRNAs (99 total) fell into two network modules that both were enriched with inflammation-related RNAs. However, treatment with the anti-inflammatory agent JQ1, an inhibitor of the bromodomain and extra-terminal (BET) protein BRD4, neutralized the LPS effect in only one module, showing little or even enhancing effect on the other. Conclusions These results provide insight into, and a resource for studying, the regulation of microglia-mediated neuroinflammation and its potential therapy by small-molecule BET inhibitors.

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The bromodomain inhibitor JQ1 up-regulates the long non-coding RNA MALAT1 in cultured human hepatic carcinoma cells

Cited by 7 publications

References 55 publications

Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells

Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells

G-quadruplex DNA contributes to RNA polymerase II-mediated 3D chromatin architecture

Analysis of differentially expressed long non-coding RNAs in LPS-induced human HMC3 microglial cells

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