Mammary Tumor-Associated RNAs Impact Tumor Cell Proliferation, Invasion, and Migration.
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.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Sarah D
SD
Diermeier
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY 11794, USA.
Kung-Chi
KC
Chang
Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
Susan M
SM
Freier
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Junyan
J
Song
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Osama
O
El Demerdash
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Alexander
A
Krasnitz
Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
Frank
F
Rigo
Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
C Frank
CF
Bennett
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.
David L
DL
Spector
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D020320:Oligoribonucleotides, Antisense / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
D020320:Oligoribonucleotides, Antisense; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm
3D organoid culture; antisense oligonucleotides; breast cancer; long non-coding RNAs; mammary tumor; transcriptome
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