Oral Presentation 16th Asian Conference on Transcription 2019

Long non-coding RNAs as regulators of gene expression in cancer (1100)

Sarah D Diermeier 1
  1. University of Otago, Dunedin, OTAGO, New Zealand

Recent genome-wide studies revealed that 1-2% of the human genome encodes for proteins, while as much as 50% of the genome can be transcribed. Of these "non-coding" transcripts, long non-coding RNAs (lncRNAs) represent the largest and most diverse class. LncRNAs can be spliced and polyadenylated, lack a significant open reading frame, and are expressed in a tissue-specific manner. They have been implicated as regulatory molecules in a variety of cellular functions, including epigenetic gene regulation, splicing, mRNA stability and translation. However, a detailed molecular mechanism is lacking for most lncRNAs.

We previously identified 30 potentially oncogenic lncRNAs in breast cancer, termed Mammary Tumour Associated RNAs(MaTARs). To functionally validate the role of MaTARs, we performed knockdown experiments and observed reduced cell proliferation, invasion and/or organoid branching in a cancer-specific context. One of the identified lncRNAs, hMaTAR17, is over-expressed in several different types of cancer compared to normal tissue. Notably, injection of antisense oligonucleotides targeting MaTAR17into a transgenic mouse model of breast cancer resulted in a significant decrease of tumour size, and increased tumour differentiation. We generated loss-of-function cell lines using CRISPR/Cas9 genome editing, and were able to reproduce the reduced proliferative potential both in vitro and in vivo.

Ongoing studies to investigate the molecular mechanism by which hMaTAR17acts include RNA-seq, single molecule RNA-FISH and Chromatin Isolation by RNA Purification in breast and colorectal cancer cells. Our results suggest that this lncRNA is likely an important driver of mammary tumour progression, and represents a promising new therapeutic target in cancer.