Journal
ONCOTARGET
Volume 7, Issue 15, Pages 20584-20596Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7828
Keywords
lncRNA; prognosis; breast cancer; biomarkers
Categories
Funding
- NIH grant [R01 CA154989]
- NSF EPSCoR Seed Grant
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Long non-coding RNAs (lncRNAs) have been recently shown to play an important role in gene regulation and normal cellular functions, and disease processes. However, despite the overwhelming number of lncRNAs identified to date, little is known about their role in cancer for vast majority of them. The present study aims to determine whether lncRNAs can serve as prognostic markers in human breast cancer. We interrogated the breast invasive carcinoma dataset of the Cancer Genome Atlas (TCGA) at the cBioPortal consisting of similar to 1,000 cases. Among 2,730 lncRNAs analyzed, 577 lncRNAs had alterations ranging from 1% to 32% frequency, which include mutations, alterations of copy number and RNA expression. We found that deregulation of 11 lncRNAs, primarily due to copy number alteration, is associated with poor overall survival. At RNA expression level, upregulation of 4 lncRNAs (LINC00657, LINC00346, LINC00654 and HCG11) was associated with poor overall survival. A third signature consists of 9 lncRNAs (LINC00705, LINC00310, LINC00704, LINC00574, FAM74A3, UMODL1-AS1, ARRDC1-AS1, HAR1A, and LINC00323) and their upregulation can predict recurrence. Finally, we selected LINC00657 to determine their role in breast cancer, and found that LINC00657 knockout significantly suppresses tumor cell growth and proliferation, suggesting that it plays an oncogenic role. Together, these results highlight the clinical significance of lncRNAs, and thus, these lncRNAs may serve as prognostic markers for breast cancer.
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