MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells

Abstract

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.

Intense light-elicited upregulation of miR-21 facilitates glycolysis and cardioprotection through Per2-dependent mechanisms

“…Data from these studies would therefore suggest that Per2-HIF1A complex is responsible for the transcriptional regulation of miR-21 during myocardial ischemia. In line with these findings, recent studies on miR-21 in small lung cancer cells revealed a similar connection between miR-21, glycolysis and HIF1A [51]. However how miR-21 controls glycolysis would need further mechanistic studies.…”

Effect of microRNA‑21 on hypoxia‑inducible factor‑1α in orthodontic tooth movement and human periodontal ligament cells under hypoxia

“…The difference in fold change may be due to the difference in concentration and potency of miR-21 mimics and miR-21 inhibitors. Previous studies have also reported that HIF-1α is regulated by other miRs (14,15,30). However, the detailed mechanism by which miR-21 regulates HIF-1α is still unknown, and the regulation may involve several signaling pathways.…”

“…Some studies indicate that miR-21 may regulate HIF-1α during cell adaptation to a hypoxic environment. In prostate cancer cells and in radioresistant non-small cell lung cancer cells, miR-21 increases the expression of HIF-1α and is involved in tumor bio-activities (14,15). Our previous study demonstrated that miR-21 is specifically expressed in PDL on the tension side and pressure side during orthodontic tooth movement in rats (16); however, it is still unclear whether miR-21 affects HIF-1α and osteogenic differentiation in PDLCs under hypoxia.…”

Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer

“…The consequential chronic inflammatory state caused by obesity facilitates immune dysregulation and angiogenesis [12]. Additionally, excess body fat creates an environment conducive to the enhanced glycolytic metabolism in cancer cells [13]. …”