4.5 Article

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

Journal

MOLECULAR MEDICINE REPORTS
Volume 14, Issue 2, Pages 1332-1338

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5394

Keywords

microRNA-155; radiosensitivity; non-small cell lung cancer; radioresistance; hexokinase 2

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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.

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