Dataset Information

Functional Modulation of Gene Expression by Ultraconserved Long Non-coding RNA TUC338 during Growth of Human Hepatocellular Carcinoma.

ABSTRACT: TUC338 is an ultraconserved long non-coding RNA that contributes to transformed cell growth in hepatocellular carcinoma (HCC). Genomic regions of TUC338 occupancy were enriched in unique or known binding motifs homologous to the tumor suppressors Pax6 and p53. Genes involved in cell proliferation were enriched within a 9-kb range of TUC338-binding sites. TUC338 RNA-based purification was used to isolate chromatin for mass spectrometry, and the plasminogen activator inhibitor-1 RNA-binding protein (PAI-RBP1) was identified as a TUC338 RNA-binding partner. The PAI-RBP1 target gene plasminogen activator inhibitor-1 (PAI-1) itself could also be post-transcriptionally regulated by TUC338. Thus modulation of transformed cell growth by TUC338 may involve binding to PAI-RBP1 as well as to sequence-defined cis-binding sites to modulate gene expression. These findings suggest that ultraconserved RNAs such as TUC338 can function in a manner analogous to transcription factors to modulate cell proliferation and transformed cell growth in HCC.

SUBMITTER: Wen HJ

PROVIDER: S-EPMC5993207 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

Functional Modulation of Gene Expression by Ultraconserved Long Non-coding RNA TUC338 during Growth of Human Hepatocellular Carcinoma.

Wen Hui-Ju HJ Walsh Michael P MP Yan Irene K IK Takahashi Kenji K Fields Alan A Patel Tushar T

iScience 20180401

TUC338 is an ultraconserved long non-coding RNA that contributes to transformed cell growth in hepatocellular carcinoma (HCC). Genomic regions of TUC338 occupancy were enriched in unique or known binding motifs homologous to the tumor suppressors Pax6 and p53. Genes involved in cell proliferation were enriched within a 9-kb range of TUC338-binding sites. TUC338 RNA-based purification was used to isolate chromatin for mass spectrometry, and the plasminogen activator inhibitor-1 RNA-binding protei ...[more]

PMID: 29888750

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Project description:Ultraconserved regions (UCRs) have been shown to originate non-coding RNA transcripts (T-UCRs) that have different expression profiles and play functional roles in the pathophysiology of multiple cancers. The relevance of these functions to the pathogenesis of bladder cancer (BlCa) is speculative. To elucidate this relevance, we first used genome-wide profiling to evaluate the expression of T-UCRs in BlCa tissues. Analysis of two datasets comprising normal bladder tissues and BlCa specimens with a custom T-UCR microarray identified ultraconserved RNA (uc.) 8+ as the most upregulated T-UCR in BlCa tissues, although its expression was lower than in pericancerous bladder tissues. These results were confirmed on BlCa tissues by real-time PCR and by in situ hybridization. Although uc.8+ is located within intron 1 of CASZ1, a zinc-finger transcription factor, the transcribed non-coding RNA encoding uc.8+ is expressed independently of CASZ1. In vitro experiments evaluating the effects of uc.8+ silencing, showed significantly decreased capacities for cancer cell invasion, migration, and proliferation. From this, we proposed and validated a model of interaction in which uc.8+ shuttles from the nucleus to the cytoplasm of BlCa cells, interacts with microRNA (miR)-596, and cooperates in the promotion and development of BlCa. Using computational analysis, we investigated the miR-binding domain accessibility, as determined by base-pairing interactions within the uc.8+ predicted secondary structure, RNA binding affinity, and RNA species abundance in bladder tissues and showed that uc.8+ is a natural decoy for miR-596. Thus uc.8+ upregulation results in increased expression of MMP9, increasing the invasive potential of BlCa cells. These interactions between evolutionarily conserved regions of DNA suggest that natural selection has preserved this potentially regulatory layer that uses RNA to modulate miR levels, opening up the possibility for development of useful markers for early diagnosis and prognosis as well as for development of new RNA-based cancer therapies.

Dataset Information

Functional Modulation of Gene Expression by Ultraconserved Long Non-coding RNA TUC338 during Growth of Human Hepatocellular Carcinoma.

Publications

Functional Modulation of Gene Expression by Ultraconserved Long Non-coding RNA TUC338 during Growth of Human Hepatocellular Carcinoma.

Similar Datasets

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