Inhibition of lactate dehydrogenase A by microRNA-34a resensitizes colon cancer cells to 5-fluorouracil
| Autor: | Xijian Zhou, Xiangyong Li, Lei Song, Haibin Zhao |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Cell Survival Colorectal cancer Lactate dehydrogenase A Down-Regulation Biology Biochemistry Cell Line Tumor Genetics medicine Humans education 3' Untranslated Regions Molecular Biology education.field_of_study Binding Sites Base Sequence L-Lactate Dehydrogenase Oncogene Cancer Cell cycle medicine.disease Molecular medicine Gene Expression Regulation Neoplastic Isoenzymes MicroRNAs Oncology Drug Resistance Neoplasm MicroRNA 34a Colonic Neoplasms Immunology Cancer cell Cancer research Molecular Medicine RNA Interference Fluorouracil Lactate Dehydrogenase 5 |
| Zdroj: | Molecular Medicine Reports. 11:577-582 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2014.2726 |
| Popis: | 5-Fluorouracil (5-FU) chemotherapy is widely used in the treatment of advanced colon cancer. However, the development of resistance to 5-FU is a significant obstacle to successful treatment. MicroRNA-34a (miR-34a) has been reported to be downregulated in a number of tumor types and has also been shown to act as a tumor suppressor. However, the mechanisms underlying the biological effects of miR-34a in chemoresistance remain unclear. The present study showed that the expression of miR-34a is downregulated in 5-FU-resistant colon cancer cells. In addition, 5-FU-resistant colon cancer cells exhibited upregulation of lactate dehydrogenase A (LDHA) expression and activity compared with parental cells. Furthermore, LDHA was shown to be a direct target of miR-34a. Overexpression of miR-34a reduced the expression of LDHA, probably through binding to the 3' untranslated region, leading to the re-sensitization of 5-FU-resistant cancer cells to 5-FU. Additionally, overexpression of LDHA rendered colon cancer cells resistant to 5-FU, suggesting that the miR-34a-induced sensitization to 5-FU is mediated through the inhibition of LDHA. In conclusion, the current study showed that miR-34a is involved in sensitivity to 5-FU in part through its effects on LDHA expression. This indicates that miR-34a‑mediated inhibition of glucose metabolism may be a therapeutic target in patients with chemoresistant colon cancer. |
| Databáze: | OpenAIRE |
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