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Insights from Global Analyses of Long Noncoding RNAs in Breast Cancer.

ABSTRACT: PURPOSE OF REVIEW:The goal of this review was to compare and contrast the results and implications from several recent transcriptomic studies that analyzed the expression of lncRNAs in breast cancer. How many lncRNAs are dysregulated in breast cancer? Do dysregulated lncRNAs contribute to breast cancer etiology? Are lncRNAs viable biomarkers in breast cancer? RECENT FINDINGS:Transcriptomic profiling of breast cancer tissues, mostly from The Cancer Genome Atlas, identified thousands of long noncoding RNAs that are expressed and dysregulated in breast cancer. The expression of lncRNAs alone can divide patients into molecular subtypes. Subsequent functional studies demonstrated that several of these lncRNAs have important roles in breast cancer cell biology. SUMMARY:Thousands of lncRNAs are dysregulated in breast cancer that can be developed as biomarkers for prognostic or therapeutic purposes. The reviewed reports provide a roadmap to guide functional studies to discover lncRNAs with critical biological functions relating to breast cancer development and progression.

SUBMITTER: Warburton AJ

PROVIDER: S-EPMC5467540 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Insights from Global Analyses of Long Noncoding RNAs in Breast Cancer.

Warburton Andrew J AJ Boone David N DN

Current pathobiology reports 20170123 1

<h4>Purpose of review</h4>The goal of this review was to compare and contrast the results and implications from several recent transcriptomic studies that analyzed the expression of lncRNAs in breast cancer. How many lncRNAs are dysregulated in breast cancer? Do dysregulated lncRNAs contribute to breast cancer etiology? Are lncRNAs viable biomarkers in breast cancer?<h4>Recent findings</h4>Transcriptomic profiling of breast cancer tissues, mostly from The Cancer Genome Atlas, identified thousand ...[more]

PMID: 28616363

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Project description:BACKGROUND:The landscape and biological functions of tumor suppressor long noncoding RNAs in breast cancer are still unknown. METHODS:Data from whole transcriptome sequencing of 33 breast specimens in the Harbin Medical University Cancer Center cohort and The Cancer Genome Atlas was applied to identify and validate the landscape of tumor suppressor long noncoding RNAs, which was further validated by The Cancer Genome Atlas pancancer data including 33 cancer types and 12,839 patients. Next, the expression model, prognostic roles, potential biological functions and epigenetic regulation of tumor suppressor long noncoding RNAs were investigated and validated in the breast cancer and pancancer cohorts. Finally, EPB41L4A-AS2 was selected to validate our novel finding, and the tumor suppressive roles of EPB41L4A-AS2 in breast cancer were examined. RESULTS:We identified and validated the landscape of tumor suppressor long noncoding RNAs in breast cancer. The expression of the identified long noncoding RNAs was downregulated in cancer tissue samples compared with normal tissue samples, and these long noncoding RNAs correlated with a favorable prognosis in breast cancer patients and the patients in the pancancer cohort. Multiple carcinogenesis-associated biological functions were predicted to be regulated negatively by these long noncoding RNAs. Moreover, these long noncoding RNAs were transcriptionally regulated by epigenetic modification, including DNA methylation and histone methylation modification. Finally, EPB41L4A-AS2 inhibited breast cancer cell proliferation, migration and invasion and induced cell apoptosis in vitro. Mechanistically, EPB41L4A-AS2, acting at least in part as a tumor suppressor, upregulated tumor suppressor gene expression. Moreover, ZNF217 recruited EZH2 to the EPB41L4A-AS2 locus and suppressed the expression of EPB41L4A-AS2 by epigenetically increasing H3K27me3 enrichment. CONCLUSIONS:This work enlarges the functional landscape of known long noncoding RNAs in human cancer and provides novel insights into the suppressive roles of these long noncoding RNAs.

Project description:Mouse and rats are staple model organisms that have been traditionally used for oncological studies; however, their short lifespan and highly prone to cancers limit their utilizationsin understanding the mechanisms of cancer resistance. In recent years, several studies of the non-standard long-lived mammalian species like naked mole rat (NMR) have provided new insights of mechanisms in natural anti-cancer. How long-lived species genetically maintain longevity and cancer-resistance remains largely elusive. To better understand the underlying anti-cancer mechanisms in long-lived mammals, we genome widely identified long noncoding RNA (lncRNA) transcripts of two longevous mammals, bowhead whale (BW, Balaena mysticetus) and Brandt's bat (BB, Myotis brandtii) and featured their sequence traits, expression patterns, and their correlations with cancer-resistance. Similar with naked mole rat (NMR, Heterocephalus glaber), the most long-lived rodent, BW and BB lncRNAs show low sequence conservation and dynamic expressions among tissues and physiological stages. By utilizing k-mers clustering, 75-136 of BW, BB and NMR lncRNAs were found in close relation (Pearson's r ≥0.9, p < 0.01) with human ageing diseases related lncRNAs (HAR-Lncs). In addition, we observed thousands of BB and BW lncRNAs strongly co-expressed (r > 0.8 or r <-0.8, p < 0.01) with potential tumour suppressors, indicating that lncRNAs are potentially involved in anti-cancer regulation in long-lived mammals. Our study provides the basis for lncRNA researches in perspectives of evolution and anti-cancer studies. Abbreviations: BW: bowhead whale; BB: Brandt's bat; NMR: naked mole rat; LLM: long-lived mammal; HTS: human tumour-suppressors; PTS: potential tumour suppressor; ARD: ageing related diseases; HAR-Lncs: lncRNAs that related with human ageing diseases; Kmer-lncs: lncRNAs in long-lived mammal species that corelated (Pearson'sr ≥0.9, p < 0.01) with the 10 HAR-Lncs by k-mers clustering; All-lncs: all the lncRNAs in long-lived mammal species; SDE-lncs: significant differentially expressed lncRNAs.

Dataset Information

Insights from Global Analyses of Long Noncoding RNAs in Breast Cancer.

Publications

Insights from Global Analyses of Long Noncoding RNAs in Breast Cancer.

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