期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 38, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13046-019-1096-0
关键词
lncRNAs; Prognosis; Tumorigenesis; Breast cancer; EPB41L4A-AS2
类别
资金
- National Natural Science Foundation of China [81602323, 81872149]
- Wu Lien-teh Science Foundation of Harbin Medical University [WLD-QN1706]
- Harbin Medical University Cancer Hospital [JCQN2018-03]
- Yong Elite Training Foundation Grant of Harbin Medical University Cancer Hospital [JY2016-02]
- Natural Science Foundation of Heilongjiang Province [H201406]
- Haiyan Fund Project of Harbin Medical University Cancer Hospital [JJQN 2018-10]
The landscape and biological functions of tumor suppressor long noncoding RNAs in breast cancer are still unknown. 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. 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. 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.
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