LINC02878/ZNF282/PYCR2 axis promotes proline synthesis and tumor progression in colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with poor survival outcomes in advanced stages due to therapy resistance and metastasis. While long non-coding RNAs (lncRNAs) are emerging as key regulators of CRC progression, their functional interplay and metabolic implications remain poorly understood. Here, we identified LINC02878 as a novel oncogenic lncRNA significantly upregulated in CRC and correlated with poor prognosis. Mechanistically, LINC02878 binds to the ZNF282 to activate PYCR2 expression, thereby enhancing proline biosynthesis and driving tumor aggressiveness. In vivo, LINC02878 knockdown suppressed subcutaneous tumor growth, reduced lung metastasis, and improved survival in xenograft models. Our study unveils the LINC02878/ZNF282/PYCR2/proline axis as a critical metabolic vulnerability in CRC, offering potential therapeutic targets for intervention.