Landscape of tumor suppressor long noncoding RNAs in breast cancer

Abstract

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. Electronic supplementary material The online version of this article (10.1186/s13046-019-1096-0) contains supplementary material, which is available to authorized users.

Investigation of the Clinical Significance and Prognostic Value of the lncRNA ACVR2B-As1 in Liver Cancer

“…A combined lncRNA-focus expression signature (LFES) that included 10 additional lncRNAs functioned as a superior unfavorable prognostic factor (AUC = 0.887) [19]. The other study, however, identified ACVR2B-AS1 as an independent favorable prognostic factor in breast cancer [20]. Our study revealed that ACVR2B-AS1 is an adverse factor in liver cancer.…”

Aberrant methylation-mediated downregulation of lncRNA CCND2 AS1 promotes cell proliferation in cervical cancer

“…Pang et al identified the landscape of tumor suppressor lncRNAs in 33 breast cancer specimens using whole transcriptome sequencing, and they validated the results with a TCGA dataset [23]. These authors identified multiple lncRNAs that were negatively regulated at the transcriptional level by epigenetic modifications such as DNA methylation and histone modification [23]. He et al found that lncRNA AFAP1-AS1 expression correlated negatively with the promoter CpG methylation status in both lung cancer cells and patient tissues, and the DNA methyltransferase inhibitor decitabine significantly increased AFAP1-AS1 expression [24].…”

“…Yang et al showed that lncRNA GAS5 expression was decreased in parallel with increased GAS5 methylation in cervical cancer cells, and forced overexpression of GAS5 inhibited the growth and metastatic behavior of the cells [22]. Pang et al identified the landscape of tumor suppressor lncRNAs in 33 breast cancer specimens using whole transcriptome sequencing, and they validated the results with a TCGA dataset [23]. These authors identified multiple lncRNAs that were negatively regulated at the transcriptional level by epigenetic modifications such as DNA methylation and histone modification [23].…”

Relevance Function of Linc-ROR in the Pathogenesis of Cancer

“…Interestingly, increasing evidence have shown that cellular events, including differentiation, proliferation, invasion, apoptosis, and migration, have all been associated with lncRNAs (Guttman et al, 2011). Additionally, there has been new evidence suggesting that lncRNAs may regulate a variety of biological and disease processes, from gene transcription and translation to post-translational modifications (Davalos and Esteller, 2019;Pang et al, 2019). More importantly, lncRNAs have been reported to be used as tumor suppressor genes or oncogenes, thus affecting the proliferation and metastasis of various types of tumors during tumorigenesis (Chen Q. N. et al, 2017;Lu et al, 2017).…”