Overexpression of LINC01354 predicts well prognosis and suppresses esophageal cancer progression

Long non-coding RNA (lncRNA) LINC01354 is involved in the progression of some cancer types, but the expression profile and prognostic value of this lncRNA in most tumor types, as well as its role and mechanism in esophageal cancer (ESCA), remain poorly characterized. Here, we identify LINC01354 as a tumor-suppressive lncRNA that inhibits ESCA progression by disrupting cell division signaling. Clinically, a pan-cancer analysis revealed widespread downregulation of LINC01354 in tumors compared to normal specimens, including ESCA and breast cancer (BRCA). Low tumor LINC01354 expression correlated with poor overall survival (OS) in ESCA and BRCA patients. In addition, the low expression of LINC01354 in tumors was validated again by two ESCA cohorts, and LINC01354 showed promising diagnostic potential. Moreover, tissue microarray (TMA) staining based on fluorescence in situ hybridization (FISH) once again confirmed the down-regulation of LINC01354 expression in ESCA. Functionally, enrichment analysis of LINC01354's co-expressed genes indicated its critical role in ESCA cell cycle regulation, and its tumor suppressive effect was verified by an in vivo tumor-bearing mouse model. The inhibition of OE-LINC01354 on ESCA cell-cycle progression was further demonstrated by flow cytometry. Mechanistically, high-depth proteomic profiling revealed that overexpression of LINC01354 alters key cell division regulators, including AURKA, AURKB, BRCA2, CCND1, CDC20, and SOX9, etc. Thus, these findings establish the LINC01354-cell division axis as a novel tumor-suppressive mechanism in ESCA and highlight its therapeutic potential.