Mir‐488 alleviates chemoresistance and glycolysis of colorectal cancer by targeting PFKFB3

BACKGROUND: Considering the boosting effect of glycolysis on tumor chemoresistance, this investigation aimed at exploring whether miR‐488/PFKFB3 axis might reduce drug resistance of colorectal cancer (CRC) by affecting glycolysis, proliferation, migration, and invasion of CRC cells. METHOD: Totally, 288 CRC patients were divided into metastasis/recurrence group (n = 107) and non‐metastasis/recurrence group (n = 181) according to their prognosis about 1 year after the chemotherapy, and their 3‐year overall survival was also tracked. Besides, miR‐488 expression was determined in peripheral blood of CRC patients and also in CRC cell lines (ie, W620, HT‐29, Lovo, and HCT116). The targeted relationship between miR‐488 and PFKFB3 was predicted by Targetscan software and confirmed by dual‐luciferase reporter gene assay. Moreover, glycolysis and drug tolerance of CRC cells lines were assessed. RESULTS: MiR‐488 expression was significantly decreased in metastatic/recurrent CRC patients than those without metastasis/recurrence (P < .05), and lowly expressed miR‐488 was suggestive of unfavorable 3‐year survival, large tumor size, poor differentiation, in‐depth infiltration, and advanced Duke stage of CRC patients (P < .05). Besides, CRC cell lines transfected by miR‐488 mimic demonstrated decreases in glucose uptake and lactate secretion, increases in oxaliplatin/5‐Fu‐sensistivity, as well as diminished capability of proliferating, invading, and migratory (P < .05), which were reversible by extra transfection of pcDNA3.1‐PFKFB3 (ie, miR‐488 mimic + pcDNA3.1‐PFKFB3 group). Finally, the mRNA level of PFKFB3 was down‐regulated by miR‐488 mimic in CRC cell lines after being targeted by it (P < .05). CONCLUSION: The miR‐488/PFKFB3 axis might clinically refine chemotherapeutic efficacy of CRC, given its modifying glycolysis and metastasis of CRC cells.