LINC00511 Promotes Breast Cancer Cell Proliferation and Invasion by Mediating MYC-Mediated Regulation of VASP.

BACKGROUND: Breast cancer remains a significant health issue, with a persistent annual increase in incidence rates and high mortality. MYC, a critical transcription factor, is often dysregulated in breast cancer, driving tumor progression. Long noncoding RNAs (lncRNAs) have emerged as key regulators in cancer, influencing gene expression through various mechanisms. This study investigates the role of lncRNAs in mediating MYC function and their impact on breast cancer progression.

METHODS: We analyzed 1212 breast cancer samples from The Cancer Genome Atlas (TCGA) database to identify lncRNAs related to MYC targets. The expression levels of lncRNAs were correlated with MYC-TARGET scores to develop a prognostic model. Functional studies were performed on LINC00511, a key lncRNA identified in the model, to elucidate its role in breast cancer progression. RNA Immunoprecipitation (RIP), Chromatin Immunoprecipitation (ChIP) and Dual-Luciferase Reporter Gene Assay assays were used to validate interactions between LINC00511, MYC, and the target gene VASP (vasodilator-stimulated phosphoprotein).

RESULTS: MYC-TARGET scores were significantly correlated with poor prognosis in breast cancer patients. We identified 38 lncRNAs associated with MYC targets, and LINC00511 was selected for further analysis due to its high expression and correlation with poor prognosis. A prognostic model composed of 5 lncRNAs (including LINC00511) was developed, with a risk score that independently predicted patient outcomes . Functional experiments showed that LINC00511 promoted breast cancer cell proliferation, migration, and invasion. Mechanistically, LINC00511 interacted with MYC to upregulate VASP expression. VASP knockdown significantly reduced breast cancer cell proliferation and migration. Overexpression of MYC rescued the inhibitory effects of LINC00511 knockdown on VASP expression and cell invasion/migration.

CONCLUSIONS: LINC00511 promotes breast cancer progression by mediating MYC to regulate VASP expression. This study highlights the importance of lncRNAs in cancer transcriptional networks and identifies LINC00511 as a potential therapeutic target for breast cancer.