title: MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis.
abstract: Nasopharyngeal carcinoma (NPC) is among the most common squamous cell carcinoma in South China and Southeast Asia. Radiotherapy is the primary treatment for NPC. However, radioresistance acts as a significant factor that limits the efficacy of radiotherapy for NPC patients. Growing evidence supports that microRNAs (miRNAs) play an important role in radiation response.
  
  
  
  Real-time quantitative PCR was used to analyze the expression of miR-19b-3p in NPC cell lines and NP69. miR-19b-3p expression profiles in NPC tissues were obtained from the Gene Expression Omnibus database. The effect of miR-19b-3p on radiosensitivity was evaluated by cell viability assays, colony formation assays and in vivo experiment. Apoptosis and cell cycle were examined by flow cytometry. Luciferase reporter assay was used to assess the target genes of miR-19b-3p. Expression of target proteins and downstream molecules were analyzed by Western blot.
  
  
  
  miR-19b-3p was upregulated in NPC and served as an independent predictor for reduced patient survival. Radioresponse assays showed that miR-19b-3p overexpression resulted in decreased sensitivity to irradiation, whereas miR-19b-3p downregulation resulted in increased sensitivity to irradiation in vitro. Moreover, miR-19b-3p decreased the sensitivity of NPC cells to irradiation in vivo. Luciferase reporter assay confirmed that TNFAIP3 was a direct target gene of miR-19b-3p. Knockdown of TNFAIP3 reduced sensitivity to irradiation, whereas upregulation of TNFAIP3 expression reversed the inhibitory effects of miR-19b-3p on NPC cell radiosensitivity. Mechanistically, we found that miR-19b-3p increased NPC cell radioresistance by activating the TNFAIP3/ NF-κB axis.
  
  
  
  miR-19b-3p contributes to the radioresistance of NPC by activating the TNFAIP3/ NF-κB axis. miR-19b-3p is a determinant of NPC radioresponse and may serve as a potential therapeutic target in NPC treatment.
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu, China.|Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.|Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.|Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.|Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Gu
authors.affiliation: Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Wu
authors.affiliation: Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.|Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Ding
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu, China.|Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Du
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu, China.|Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.
authors.forename: Lu-Xi
authors.initials: LX
authors.lastname: Qian
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu, China.|Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Lu
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu, China. hexiaBM@163.com.|Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu, 210000, China. hexiaBM@163.com.
authors.forename: Xia
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000528:radiation effects; D016019:Survival Analysis; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: Apoptosis; Nasopharyngeal carcinoma; Radiosensitivity; microRNA-19b-3p