title: Hypofractionated radiotherapy induces miR-34a expression and enhances apoptosis in human nasopharyngeal carcinoma cells.
abstract: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Long
authors.affiliation: Department of Otolaryngology (ENT), The Fifth Hospital of Wuhan, Wuhan, Hubei 430051, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430051, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Tao
authors.affiliation: Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430051, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Zezhang
authors.initials: Z
authors.lastname: Tao
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D002277:Carcinoma; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53