PMID- 25231528 OWN - NLM STAT- MEDLINE DCOM- 20150617 LR - 20190221 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 34 IP - 5 DP - 2014 Nov TI - Hypofractionated radiotherapy induces miR-34a expression and enhances apoptosis in human nasopharyngeal carcinoma cells. PG - 1388-94 LID - 10.3892/ijmm.2014.1937 [doi] AB - Nasopharyngeal carcinoma (NPC) is a relatively radiosensitive disease. However, the therapeutic effects of radiotherapy are not always satisfactory due to radioresistance. The hypofractionated schema is currently widely used in clinical practice. In the present study, we investigated the effects of hypofractionated radiotherapy on NPC cells and explored the mechanisms involved. In addition, we aimed to determine the role of miR-34a in the effects of hypofractionated radiotherapy and whether these effects occur in a p53-dependent manner. For this purpose, we used CNE1 and CNE2 NPC cells which were subjected to hyperfractionated and hypofractionated radiotherapy. The viability of the cells was measured by MTT assay and acridine orange (AO) and ethidium bromide (EB) staining was used to observe morphological changes. In addition, Annexin V-propidium iodide (PI) staining and flow cytometry were used to determine the number of apoptotic cells and mRNA and protein expression was measured by qPCR and western blot analysis, respectively. The results revealed that hypofractionated radiotherapy enhanced apoptosis and increased the expression of miR-34a and p53 in the NPC cells. In addition, it stimulated p53 promoter activity and downregulated the protein expression of c-Myc in the human NPC cells. Furthermore, the knockdown of miR-34a suppressed the growth inhibitory effects induced by hypofractionated radiotherapy. Thus, our results suggest that the enhanced apoptosis of NPC cells may be associated with the miR-34a-mediated suppression of c-Myc in a p53-dependent manner. FAU - Long, Zhixiong AU - Long Z AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China. FAU - Wang, Bin AU - Wang B AD - Department of Otolaryngology (ENT), The Fifth Hospital of Wuhan, Wuhan, Hubei 430051, P.R. China. FAU - Tao, Dan AU - Tao D AD - Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430051, P.R. China. FAU - Huang, Ying AU - Huang Y AD - Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430051, P.R. China. FAU - Tao, Zezhang AU - Tao Z AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China. LA - eng PT - Journal Article DEP - 20140917 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (MIRN34 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (Tumor Suppressor Protein p53) SB - IM MH - Apoptosis/*radiation effects MH - Carcinoma MH - Cell Line, Tumor MH - Cell Survival/radiation effects MH - Down-Regulation MH - Gene Expression Regulation, Neoplastic/*radiation effects MH - Humans MH - MicroRNAs/genetics/*metabolism MH - Nasopharyngeal Carcinoma MH - Nasopharyngeal Neoplasms/*genetics/*radiotherapy MH - Promoter Regions, Genetic MH - Proto-Oncogene Proteins c-myc/genetics/metabolism MH - Radiation Tolerance MH - Tumor Suppressor Protein p53/genetics/metabolism EDAT- 2014/09/19 06:00 MHDA- 2015/06/18 06:00 CRDT- 2014/09/19 06:00 PHST- 2014/04/26 00:00 [received] PHST- 2014/09/10 00:00 [accepted] PHST- 2014/09/19 06:00 [entrez] PHST- 2014/09/19 06:00 [pubmed] PHST- 2015/06/18 06:00 [medline] AID - 10.3892/ijmm.2014.1937 [doi] PST - ppublish SO - Int J Mol Med. 2014 Nov;34(5):1388-94. doi: 10.3892/ijmm.2014.1937. Epub 2014 Sep 17.