Triple-negative breast cancer (TNBC), an aggressive and hard-to-treat form of breast cancer, has long challenged researchers due to the absence of effective targeted therapies. Now, findings from Cold Spring Harbor Laboratory in New York State have revealed a potentially significant contributor to TNBC biology: a little-studied long non-coding RNA (lncRNA) known as LINC01235.
Breast cancer is among the most common malignancies in women worldwide, and TNBC accounts for approximately 10 to 15 percent of cases. It is disproportionately diagnosed in younger women and those of African American descent. While many forms of breast cancer benefit from targeted treatments, TNBC lacks such options, making basic research crucial.
The study was led by Professor David Spector and graduate student Wenbo Xu. They discovered that LINC01235, previously associated with gastric cancer, also plays a role in TNBC by regulating a gene called NFIB, which is already linked to this cancer subtype.
Using CRISPR gene-editing and antisense knockdown techniques in tumour organoids and cancer cells, the researchers showed that lowering LINC01235 levels suppressed NFIB expression and inhibited TNBC organoid growth. Further analysis suggested that this interaction affects the NOTCH signalling pathway, known to be involved in cancer cell proliferation.
The NOTCH signalling pathway is a fundamental cell communication system that regulates how cells develop, differentiate, and interact with their environment. It is evolutionarily conserved and plays a crucial role in embryonic development, tissue homeostasis, and cell fate decisions. In TNBC aberrant NOTCH signalling can lead to uncontrolled cell proliferation, resistance to apoptosis and enhanced tumour invasiveness.
Very little is known about NFIB’s function in this context and even less about LINC01235.
“The goal here is to understand mechanisms by which the cell functions and how disease states take over those functions, perhaps by up-regulating or down-regulating an RNA molecule,” Spector noted.
While these results are at a preliminary stage, the work points to the promise of lncRNAs as potential therapeutic targets. LINC01235 may yet prove to be a vital step towards effective treatment options for TNBC.
For further reading please visit: 10.1158/1541-7786.MCR-24-1143