Noncoding RNA transcription at enhancers and genome folding in cancer

Isoda, Takeshi; Morio, Tomohiro; Takagi, Motoki

doi:10.1111/cas.14107

Cited by 12 publications

(10 citation statements)

References 74 publications

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“…In line with the critical roles of enhancers in the orchestration of gene expression in and outside of insulated chromatin domains [topologically associating domains (TADs); Fanucchi and Mhlanga, 2017], nucleotide variants and disruptions affecting enhancers, and potentially the transcription of eRNAs and lncRNAs generated from these regions, have been implicated in various diseases. This ranges from autoimmune diseases to mental disorders and cancer (Farh et al, 2015;Javierre et al, 2016;Teppo et al, 2016;Ren et al, 2017;Hauberg et al, 2019;Isoda et al, 2019;Lewis et al, 2019;Chen et al, 2020b;Yamagata et al, 2020). Thus, beyond lncRNAs encoded within coding gene regions or seemingly empty genomic space, genetic variation in transcribed regulatory DNA units, such as enhancers, contributes to human diseases.…”

Section: Discussionmentioning

confidence: 99%

“…In the context of cardiovascular diseases, for instance, SNPs affecting the well-studied lncRNA ANRIL were pointed out (Lozano-Vidal et al, 2019). Furthermore, aberrations in non-coding genome regions corresponding to transcribed enhancers potentially contribute to human diseases (Isoda et al, 2019). A closer investigation of mutations and polymorphisms affecting the transcription or function of non-coding RNAs generated from such regulatory elements might contribute additional insights into the roles of non-coding genome alterations in human diseases (see Discussion).…”

Section: Linc-hellpmentioning

confidence: 99%

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Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

et al. 2020

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The classic understanding of molecular disease-mechanisms is largely based on protein-centric models. During the past decade however, genetic studies have identified numerous disease-loci in the human genome that do not encode proteins. Such non-coding DNA variants increasingly gain attention in diagnostics and personalized medicine. Of particular interest are long non-coding RNA (lncRNA) genes, which generate transcripts longer than 200 nucleotides that are not translated into proteins. While most of the estimated ~20,000 lncRNAs currently remain of unknown function, a growing number of genetic studies link lncRNA gene aberrations with the development of human diseases, including diabetes, AIDS, inflammatory bowel disease, or cancer. This suggests that the protein-centric view of human diseases does not capture the full complexity of molecular patho-mechanisms, with important consequences for molecular diagnostics and therapy. This review illustrates well-documented lncRNA gene aberrations causatively linked to human diseases and discusses potential lessons for molecular disease models, diagnostics, and therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Linc-hellpmentioning

confidence: 99%

Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

et al. 2020

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“…In addition, eRNA ARIEL boosts E–P interactions, thereby activating ARID5B expression and promoting the TAL1-induced transcription of the MYC oncogene [ 108 ]. eRNA can also regulate 3D chromatin architecture and, therefore, E–P interactions in solid tumour development (see review by Isoda et al [ 109 ]). In solid tumours, intrigued by more than 100 single nucleotide polymorphism (SNP) risk loci related to colorectal cancer revealed by genome-wide association studies (GWAS), Tian et al [ 110 , 111 ] found that these risk loci drive long-range E–P interactions, regulating several oncogenes including ATF1, E2F1, FADS2, and AP002754.2.…”

Section: Types Of 3d Chromatin Architecturementioning

confidence: 99%

3D chromatin architecture and transcription regulation in cancer

2022

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Chromatin has distinct three-dimensional (3D) architectures important in key biological processes, such as cell cycle, replication, differentiation, and transcription regulation. In turn, aberrant 3D structures play a vital role in developing abnormalities and diseases such as cancer. This review discusses key 3D chromatin structures (topologically associating domain, lamina-associated domain, and enhancer–promoter interactions) and corresponding structural protein elements mediating 3D chromatin interactions [CCCTC-binding factor, polycomb group protein, cohesin, and Brother of the Regulator of Imprinted Sites (BORIS) protein] with a highlight of their associations with cancer. We also summarise the recent development of technologies and bioinformatics approaches to study the 3D chromatin interactions in gene expression regulation, including crosslinking and proximity ligation methods in the bulk cell population (ChIA-PET and HiChIP) or single-molecule resolution (ChIA-drop), and methods other than proximity ligation, such as GAM, SPRITE, and super-resolution microscopy techniques.

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“…Non-coding are the heterogeneous classes of RNA transcripts, including long noncoding RNA (lncRNAs), microRNAs (miRNAs) and others, which exert oncogenic and tumorgenicity functions 25 , 26 . Accumulating studies have shown that noncoding RNA, mainly lncRNAs (>200 nucleotides) and miRNAs (19-25 nt) have been aberrantly expressed in distinct human malignancies, and are being considered as an important emerging key player in the cancer paradigm.…”

Section: Introductionmentioning

confidence: 99%

SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis

Feng¹,

Bhandari²,

Liu³

et al. 2021

J. Cancer

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Background: Hepatoblastoma is a common hepatic tumor occurring in children between 0-5 years. Accumulating studies have shown lncRNA's potential role in distinct cancer progression and development, including hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated with the progression of distinct human cancers, but, its specific molecular mechanisms in hepatoblastoma is not unknown. Methods: In this study, we estimated SNHG9 expression in hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated SNHG9 expression in hepatoblastoma cell lines and then determined cell proliferation (CCK-8), colony formation, and cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pull down and Spemann's Pearson correlation coefficient assay were performed to establish the interaction between SNHG9, WNt3a and miR-23a-5p. A xenograft in-vivo tumorgenicity test was performed to elucidate the role of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drug resistance in hepatoblastoma was also determined. Results: SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogenic activity while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. The xenograft tumorgenicity test showed SNHG9 downregulation significantly inhibited the tumor growth in BALB/c mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma. Conclusion:We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.

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Noncoding RNA transcription at enhancers and genome folding in cancer

Cited by 12 publications

References 74 publications

Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

3D chromatin architecture and transcription regulation in cancer

SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis

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