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Cell Rep. 2016 Sep 27;17(1):261-274. doi: 10.1016/j.celrep.2016.08.081.

Mammary Tumor-Associated RNAs Impact Tumor Cell Proliferation, Invasion, and Migration.

Author information

1
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
2
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY 11794, USA.
3
Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
4
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
5
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: spector@cshl.edu.

Abstract

Long non-coding RNAs (lncRNAs) represent the largest and most diverse class of non-coding RNAs, comprising almost 16,000 currently annotated transcripts in human and 10,000 in mouse. Here, we investigated the role of lncRNAs in mammary tumors by performing RNA-seq on tumor sections and organoids derived from MMTV-PyMT and MMTV-Neu-NDL mice. We identified several hundred lncRNAs that were overexpressed compared to normal mammary epithelium. Among these potentially oncogenic lncRNAs we prioritized a subset as Mammary Tumor Associated RNAs (MaTARs) and determined their human counterparts, hMaTARs. To functionally validate the role of MaTARs, we performed antisense knockdown and observed reduced cell proliferation, invasion, and/or organoid branching in a cancer-specific context. Assessing the expression of hMaTARs in human breast tumors revealed that 19 hMaTARs are significantly upregulated and many of these correlate with breast cancer subtype and/or hormone receptor status, indicating potential clinical relevance.

KEYWORDS:

3D organoid culture; antisense oligonucleotides; breast cancer; long non-coding RNAs; mammary tumor; transcriptome

PMID:
27681436
PMCID:
PMC5079290
DOI:
10.1016/j.celrep.2016.08.081
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

D.L.S. receives research support from, and is a consultant to, Ionis Pharmaceuticals.

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