Xu, Wenbo, Bhatia, Sonam, Sahin, Yunus, Spector, David L (June 2025) LINC01235 is an Upstream Regulator of the NFIB Gene and the NOTCH Pathway in Triple Negative Breast Cancer. Molecular Cancer Research. ISSN 1541-7786
Abstract
We identified a long non-coding RNA (lncRNA), LINC01235, with significant enrichment in luminal progenitor (LP)-like cells in triple negative breast cancer organoids and cell lines. Antisense-mediated knockdown or genetic knockout of LINC01235 in TNBC cell lines led to a decline in cell proliferation and adversely impacted the ability to form organoids. A comprehensive co-expression analysis, leveraging TCGA data, revealed a distinct correlation between LINC01235 expression and the expression of NFIB, a neighboring gene encoding a transcription factor. Subsequent CRISPR knockout or ASO-mediated knockdown studies demonstrated an upstream regulatory role of LINC01235 over NFIB. Moreover, our investigations demonstrated that LINC01235 regulates the NOTCH pathway through NFIB, and ChIRP-qPCR results indicated the direct binding of LINC01235 to the NFIB promoter. Our findings demonstrate that LINC01235 positively regulates NFIB transcription, which in turn modulates the NOTCH pathway, influencing LP-like cell proliferation in breast cancer progression. This study highlights a pivotal role of LINC01235 in TNBC and its potential as a therapeutic target. Implications: This study demonstrates the central role of LINC01235 as an upstream positive regulator of NFIB and the NOTCH signaling pathway to induce the production of luminal progenitor-like cells in TNBC.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > breast cancer diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL labs > Spector lab CSHL Cancer Center Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 30 June 2025 |
| Date Deposited: | 08 Jul 2025 15:49 |
| Last Modified: | 08 Jul 2025 15:49 |
| PMCID: | PMC12221212 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41899 |
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