LINC01235 Emerges as Key Driver in Aggressive Triple-Negative Breast Cancer

In a significant breakthrough, researchers at Cold Spring Harbor Laboratory have identified the long non-coding RNA molecule LINC01235 as a critical factor in the progression of aggressive triple-negative breast cancer (TNBC). This discovery, published in the *Molecular Cancer Research* journal on July 9, 2025, sheds light on the complex biology of TNBC, which continues to pose a significant challenge for effective treatment. TNBC, accounting for 10 to 15 percent of all breast cancer cases, is particularly aggressive and disproportionately affects younger women and African American women, underscoring the urgency for targeted therapies in this area.

The study, led by Professor David Spector and graduate student Wenbo Xu, began with RNA sequencing conducted on human breast tumor organoids—3D models that replicate the biology of tumors in patients. Their investigation revealed a notable correlation between the expression levels of LINC01235 and NFIB, a gene previously linked to TNBC. Despite NFIB's established role, LINC01235 had remained largely unstudied until now.

"We came upon this interesting story of where it sits in the genome and the gene it regulates," stated Professor Spector. The research team utilized CRISPR technology to effectively knock out LINC01235 in cancer cells and applied antisense molecules to reduce its levels in both cancer cells and organoids. The results were telling; reducing LINC01235 led to decreased NFIB expression and significantly suppressed the formation of TNBC organoids, indicating a direct role in cancer progression.

Wenbo Xu elaborated, "Our findings demonstrate that LINC01235 positively regulates NFIB transcription, which modulates the NOTCH pathway, influencing cell proliferation in TNBC progression." These advancements not only highlight the functional role of lncRNAs in cancer biology but also suggest potential new avenues for targeted therapies against TNBC, which has no effective existing treatments.

The research underscores the importance of understanding the mechanisms by which cells function, especially in disease states where non-coding RNAs may be up- or down-regulated. Professor Spector emphasized the broader significance of this research, stating, "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."

The identification of LINC01235 as a driver of TNBC progression represents a promising step toward developing targeted therapies for one of the deadliest subtypes of breast cancer. The ongoing research will investigate how these findings can be translated into clinical applications, offering hope to countless individuals affected by this aggressive cancer type.

The implications of this study extend beyond just the identification of LINC01235, as it reflects a broader trend in cancer research focusing on the role of non-coding RNAs in tumor biology. As researchers continue to explore the intricate relationships between various RNA molecules and cancer pathways, the potential for new therapeutic strategies against challenging cancers like TNBC may become a reality.

In conclusion, the findings from Cold Spring Harbor Laboratory not only enhance our understanding of TNBC but also pave the way for innovative treatment strategies that could significantly impact the lives of patients battling this formidable disease. Continued research efforts are essential to fully realize the therapeutic potential of LINC01235 and similar molecules in the fight against breast cancer.