Abstract
Approximately 15-20% of breast cancers are triple-negative, an aggressive subtype of
breast cancer that lacks progesterone receptors, oestrogen receptors, and human epidermal
growth factor 2 (HER2) receptors. Therefore, treatment options for triple-negative breast
cancer (TNBC) are minimal due to the lack of these receptors that are commonly targeted.
Long non-coding RNAs (lncRNAs) have been discovered to contribute to the growth and
survival of cancers. LncRNAs are classified as being over 200 nucleotides long and have
no significant open reading frame. Their key roles in regulating cancer related pathways,
and the dysregulation of their expression in multiple malignancies suggests that lncRNAs
may be utilised as biomarkers and/or therapeutic targets in cancer.
This study proposes a newly discovered molecule, the long non-coding RNA lncTNBC1,
to be involved in cell growth of TNBC. MDA-MB-231-LM2 cells are derived from triple-
negative MDA-MB-231 parental cells and were chosen to study for their propensity to
metastasize to the lungs. Loss of function (LOF) models of lncTNBC1 was established
using both CRISPR interference (CRISPRi) and siRNA transfection approaches. Our
analysis revealed that knockdown of lncTNBC1 significantly reduced cell migration,
indicating that lncTNBC1 is a key regulator of this process. We then investigated the
molecular mechanism of lncTNBC1 employing an MS2-TRAP pull down assay to identify
its RNA/protein partners via RNAseq and mass spectrometry. Pathway analysis of these
interactive partners revealed key processes related to cell migration, further supporting its
role as an enhancer of this function in TNBC.
This study has allowed for the investigation of lncTNBC1 as a potential driver of TNBC
growth. Findings from this study, as well future studies on this molecule, will make it
possible to discover alternative therapeutic targets that improve the clinical diagnosis and
management of TNBC patients