Recent genome-wide studies revealed that only 2% of the human genome encodes for mRNAs that are translated into proteins while as much as 80% of the genome can be transcribed. Of these non-coding transcripts, long non-coding RNAs (lncRNAs) represent the largest and most diverse class, 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 long non-coding transcripts that were over-expressed compared to the 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 up-regulated and many of these correlate with breast cancer subtype and/or hormone receptor status, indicating potential clinical relevance. SOURCE: Sarah,D,Diermeier (sdiermei@cshl.edu) - Spector Cold Spring Harbor Laboratory

Pluto Bioinformatics

GSE72823: Mammary Tumor Associated RNAs impact tumor cell proliferation, invasion and migration