GLUT5 regulation by AKT1/3-miR-125b-5p downregulation induces migratory activity and drug resistance in TLR-modified colorectal cancer cells
| Autor: | Ga-Bin Park, Daejin Kim, Jee-Yeong Jeong |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Small interfering RNA Colorectal cancer Down-Regulation Antineoplastic Agents 03 medical and health sciences Enzyme activator 0302 clinical medicine Downregulation and upregulation Cell Movement medicine Humans Gene silencing Chemistry Glucose Transporter Type 5 Lipogenesis Toll-Like Receptors Cancer General Medicine Transfection medicine.disease Enzyme Activation MicroRNAs 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell Cancer research Colorectal Neoplasms Glycolysis HT29 Cells Proto-Oncogene Proteins c-akt |
| Zdroj: | Carcinogenesis. 41:1329-1340 |
| ISSN: | 1460-2180 0143-3334 |
| Popis: | In cancer, resistance to chemotherapy is one of the main reasons for therapeutic failure. Cells that survive after treatment with anticancer drugs undergo various changes, including in cell metabolism. In this study, we investigated the effects of AKT-mediated miR-125b-5p alteration on metabolic changes and examined how these molecules enhance migration and induce drug resistance in colon cancer cells. AKT1 and AKT3 activation in drug-resistant colon cancer cells caused aberrant downregulation of miR-125b-5p, leading to GLUT5 expression. Targeted inhibition of AKT1 and AKT3 restored miR-125b-5p expression and prevented glycolysis- and lipogenesis-related enzyme activation. In addition, restoring the level of miR-125b-5p by transfection with the mimic sequence not only significantly blocked the production of lactate and intracellular fatty acids but also suppressed the migration and invasion of chemoresistant colon cancer cells. GLUT5 silencing with small interfering RNA attenuated mesenchymal marker expression and migratory activity in drug-resistant colon cancer cells. Additionally, treatment with 2,5-anhydro-d-mannitol resensitized chemoresistant cancer cells to oxaliplatin and 5-fluorouracil. In conclusion, our findings suggest that changes in miR-125b-5p and GLUT5 expression after chemotherapy can serve as a new marker to indicate metabolic change-induced migration and drug resistance development. |
| Databáze: | OpenAIRE |
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