The ceRNA network of LINC00536/miR-204-5p/TGFBR2: A novel therapeutic target for breast cancer diagnosis and treatment.

[BACKGROUND] Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to regulate tumor progression, yet the role of LINC00536 in breast cancer (BC) remains unclear. This study investigates the oncogenic function,potential tumor microenvironment (TME) relevance, and molecular mechanism of LINC00536 in BC.

[METHODS] A pan-cancer analysis using TCGA/GTEx databases evaluated LINC00536 expression and its prognostic relevance. Functional assays (CCK-8, EdU, wound healing, colony formation) and qRT-PCR were performed in BC cell lines. Dual-luciferase reporter, Western blot, and ELISA validated the LINC005iR-204-5p/TGFBR2 axis and TGF-β pathway activation. Nude mouse xenograft and lung metastasis models assessed in vivo tumorigenicity.

[RESULTS] LINC00536 was overexpressed in BC tissues/cell lines and its expression correlated with a poor prognosis. High LINC00536 levels were associated with elevated stromal/immune scores and immune checkpoint gene expression, suggesting a potential role in TME modulation. Mechanistically, LINC00536 sponged miR-204-5p, thereby upregulating TGFBR2, which activated TGF-β signaling and induced epithelial-mesenchymal transition (EMT). In vitro, LINC00536 promoted proliferation, migration, and EMT, while in vivo, it accelerated tumor growth and lung metastasis (p < 0.05). Time-dependent TGF-β activation dynamics confirmed pathway regulation via the LINC00536/miR-204-5p/TGFBR2 axis.

[CONCLUSIONS] LINC00536 promotes BC progression and activates TGF-β signaling via miR-204-5p/TGFBR2, with its expression correlating with features of the TME, establishing its potential as a diagnostic/prognostic biomarker and therapeutic target.