MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells
| Autor: | Xue Dou, Hongjiang Yan, Renben Wang, Linzhi Jin, Jiang Shumei, Dong Chen |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms Cell Biology Biochemistry Radiation Tolerance 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Radioresistance Carcinoma Non-Small-Cell Lung Cell Line Tumor microRNA Genetics medicine Humans RNA Neoplasm Molecular Biology A549 cell Cell cycle Hypoxia-Inducible Factor 1 alpha Subunit Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis Immunology Cancer cell Cancer research Molecular Medicine Glycolysis |
| Zdroj: | Molecular medicine reports. 13(5) |
| ISSN: | 1791-3004 |
| Popis: | Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer‑associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)‑21 in the development of radiation resistance in non‑small cell lung cancer cells. A radiation‑resistant cell line was generated from A549 cells. Significant upregulation of miR‑21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR‑21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia‑inducible factor‑1α (HIF1α) was upregulated by miR‑21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR‑21‑inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR‑21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs. |
| Databáze: | OpenAIRE |
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