LINC01235 identified as driver of aggressive breast cancer

Breast cancer remains one of the most common cancers among women in the United States and, thanks to decades of research, one of the most treatable. However, triple-negative breast cancer (TNBC), a particularly aggressive form, continues to challenge scientists. TNBC accounts for 10 to 15 percent of all breast cancer cases and disproportionately affects younger women and African American women. Currently, there are no effective targeted therapies for this subtype of cancer.

A recent breakthrough from Cold Spring Harbor Laboratory (CSHL) offers fresh insight into TNBC’s biology, potentially allowing for new treatments. The discovery, led by Professor David Spector and graduate student Wenbo Xu, was published in Molecular Cancer Research.

Investigating the role of long non-coding RNAs in cancer

Professor Spector’s team focuses on long non-coding RNAs (lncRNAs) – a class of RNA molecules that do not code for proteins but are increasingly recognised as key players in cancer development. Their latest study identified a rarely studied lncRNA called LINC01235 – previously linked to gastric cancer – as an important factor in TNBC.

The discovery began with RNA sequencing performed on human breast tumour organoids – miniature 3D cancer models that mimic the biology of tumours in patients. Project lead Wenbo Xu, reviewed data from The Cancer Genome Atlas – a comprehensive cancer patient database with over 11,000 cases. Xu noticed a correlation between LINC01235 expression and NFIB, a gene previously associated with TNBC.

Still, very little was known about NFIB, and almost nothing about LINC01235. So, the team decided to delve deep and ask how does it work in the cell? and what processes might it be involved in?

“We came upon this interesting story of where it sits in the genome and the gene it regulates,” said Spector.

Experimental evidence links LINC01235 to TNBC progression

To investigate, the researchers used CRISPR technology to knock out LINC01235 in cancer cells. They also used antisense molecules to reduce LINC01235 levels in cancer cells and organoids. In both experiments, lowering LINC01235 led to decreased NFIB expression. Crucially, this reduction suppressed the formation of TNBC organoids, suggesting a direct role in cancer progression.

“Our findings demonstrate that LINC01235 positively regulates NFIB transcription,” Xu said. “This modulates the NOTCH pathway, influencing cell proliferation in TNBC progression.”

A step toward future therapies targeting non-coding RNAs

While more research is necessary to translate these findings into treatments, the study highlights the promising role of lncRNAs in combating TNBC. Professor Spector emphasised the broader significance: “The goal here is to understand mechanisms by which the cell functions and how disease states take over those functions, perhaps by up-regulating an RNA molecule or down-regulating an RNA molecule. Our long-term goal is to try to find a lncRNA or multiple lncRNAs that may eventually be therapeutic targets.”

This discovery represents a step toward targeted therapies for  one of the deadliest breast cancer subtypes.