A perspective analysis: microRNAs, glucose metabolism, and drug resistance in colon cancer stem cells

Background: Metabolism drives the stemness of cancer stem cells (CSCs), affecting, in turn, tumor heterogeneity, metastatic potential, and therapy resistance. Therefore, considerable attention is paid to the report that glucose metabolism regulates the expression of the anti-apoptotic microRNA in liver cancer cells, miR-483-3p. Nevertheless, little is known about the function of miR-483-3p and glucose metabolism during tumor formation from CSCs. Since genetic marks and biological effects correlate this miRNA with colon cancer (CC), we investigated the therapeutic potential of targeting miR-483-3p by using the anti-glucose metabolism 2-deoxyglucose (2-DG) molecule in tumor Xenograft mouse model originating from two different Colon Cancer Stem Cell lines (CCSC lines). Results: 2-DG decreases the expression of miR-483-3p in vitro and in vivo in one CCSC line. However, the treatment did not affect the tumor development in Xenograft immune-compromised tumor models. Xenograft tumors display strong increases of miR-483-3p when compared to the CCSC line of origin, suggesting possible distinctive roles of the miR, depending on the differentiation state of the cells. Conclusion: 2-DG treatment does not affect CCSCs during tumor formation in immunocompromised in vivo models despite its ability to increase the CCSC apoptotic rate in vitro, and decrease miR-483-3p expression both in vitro and in vivo experimental conditions.