LINC01764 promotes colorectal cancer cells proliferation, metastasis, and 5-fluorouracil resistance by regulating glucose and glutamine metabolism via promoting c-MYC translation.

Few biomarkers are available for predicting chemotherapeutic response and prognosis in colorectal cancer (CRC). Long-noncoding RNAs (lncRNAs) are essential for CRC development and growth. Therefore, studying lncRNAs may reveal potential predictors of chemotherapy response and prognosis in CRC. LINC01764 was analyzed using datasets from Fudan University Shanghai Cancer Center's advanced CRC patients' RNA-seq and The Cancer Genome Atlas datasets. Gene set enrichment analysis was employed to detect related pathways. Cotransfection experiments, RNA pulldown assays, RNA-binding protein immunoprecipitation, protein synthesis activity, and dual-luciferase reporter assays were performed to determine interactions among LINC01764, hnRNPK, and c-MYC. High LINC01764 expression correlates with metastasis, a poor response to FOLFOX/XELOX chemotherapy, and a poor prognosis in CRC. LINC01764 enhance glycolysis and glutamine metabolism to promote CRC cells proliferation, metastasis, and 5-fluorouracil (5-FU) resistance. LINC01764 specifically binds to hnRNPK, facilitating its interaction with c-MYC mRNA and promoting internal ribosome entry site (IRES)-dependent translation of c-MYC, thereby exerting oncogenic effects. LINC01764 induced 5-FU chemoresistance by upregulating the c-MYC, glucose, and glutamine metabolism pathways, which downregulated , crucial for activating 5-FU. Conclusively, LINC01764 promotes CRC progression and 5-FU resistance through hnRNPK-mediated-c-MYC IRES-dependent translational regulation, which suggests its potential as a predictor of CRC chemotherapy response and prognosis.