A novel miR-490-3p/hnRNPA1-b/PKM2 axis intermediates the Warburg effect and proliferation of colon cancer via PI3K/AKT pathway

Abstract

Background Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance Warburg effect and promote colon cancer (CC) proliferation, but the role and mechanism of miR-490-3p/hnRNPA1-b/PKM2 axis in CC are not yet elucidated. Methods Paraffin-embedded pathological sections from 220 colon cancer patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using qPCR, while differences in protein expression were analyzed using Western blot. Cell proliferation was evaluated using CCK8 and EdU assays, and cell cycle and apoptosis were assessed using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. Warburg effect was evaluated through glucose uptake and lactic acid production assays. Results The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen among different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-140-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect. Conclusion These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.