Inhibition of microRNA-155 sensitizes lung cancer cells to irradiation via suppression of HK2-modulated glucose metabolism.

Abstract

MicroRNAs (miRNAs) are small non-coding regulatory RNAs, which are involved in the post-transcriptional regulation of gene expression. miRNA (miR)-155, which has previously been reported to be overexpressed in lung cancer, is correlated with poor patient prognosis. The present study aimed to investigate the effects of miR‑155 on the radiosensitivity of human non‑small cell lung cancer (NSCLC) cells. To explore the roles of miRNAs in the regulation of irradiation sensitivity of human lung cancer cells, the expressions of miR‑155 in response to irradiation, have been studied by RT‑qPCR, and the putative direct target of miR‑155 was identified by western blot and luciferase assays. The results of the present study revealed that the expression of miR‑155 was induced by irradiation, thus suggesting a positive correlation between miR‑155 and radiosensitivity. Furthermore, overexpression of miR‑155 rendered lung cancer cells resistant to irradiation. In addition, hexokinase 2 (HK2) was identified as an indirect target of miR‑155; exogenous overexpression of miR‑155 upregulated the expression of HK2, whereas inhibition of miR‑155 by antisense miRNA suppressed HK2 expression. In addition, HK2‑modulated glucose metabolism was significantly upregulated by overexpression of miR‑155. Notably, inhibition of miR‑155 sensitized lung cancer cells to irradiation via suppression of glucose metabolism. In conclusion, the present study reported a novel function for miR‑155 in the regulation of NSCLC cell radiosensitivity, thus suggesting that miR‑155 may be considered a therapeutic target for the development of anticancer drugs.

• Authors: Xin Lv, Li Yao, Jianli Zhang, Ping Han, Cuiyun Li
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 14 Issue 2 Pg. 1332-8 (Aug 2016) ISSN: 1791-3004 [Electronic] Greece
• PMID: 27315591 (Publication Type: Journal Article)

Chemical References

• MIRN155 microRNA, human
• MicroRNAs
• HK2 protein, human
• Hexokinase
• Glucose

Topics

• Cell Line, Tumor
• Cell Proliferation
• Cell Survival (genetics, radiation effects)
• Dose-Response Relationship, Radiation
• Gene Expression Regulation, Neoplastic
• Glucose (metabolism)
• Glycolysis
• Hexokinase (genetics, metabolism)
• Humans
• Lung Neoplasms (genetics, metabolism)
• MicroRNAs (genetics)
• RNA Interference
• Radiation Tolerance (genetics)
• Radiation, Ionizing