title: Protein N-arginine methyltransferase 5 promotes the tumor progression and radioresistance of nasopharyngeal carcinoma.
abstract: Radiotherapy resistance is the main cause of the the poor prognosis of some nasopharyngeal carcinoma (NPC) patients. Yet, the exact mechanism is still elusive. In the present study, we explored the clinical and biological role of protein arginine methyltransferase 5 (PRMT5) in NPC. Our results revealed that PRMT5 was overexpressed in NPC tissues when compared with that in adjacent non-tumor tissues by quantitative RT-PCR and immunoblotting. High expression of PRMT5 was correlated with adverse outcomes of NPC patients as determined by the scoring of a tissue microarray. Silencing of PRMT5 promoted the radiosensitivity of 5-8F and CNE2 cells as determined by cell proliferation and colony formation assays. Furthermore, fibroblast growth factor receptor 3 (FGFR3) was identified as one of the downstream targets of PRMT5, and the silencing of PRMT5 decreased the mRNA and protein levels of FGFR3 in the 5-8F and CNE2 cells. Silencing of FGFR3 induced similar phenotypes as the inhibition of PRMT5, and re-expression of FGFR3 in 5-8F/shPRMT5 and CNE2/shPRMT5 cells restored the proliferation and colony formation ability induced by irradiation exposure. Our results indicate that PRMT5 is a marker of poor prognosis in NPC patients. PRMT5 promoted the radioresistance of NPC cells via targeting FGFR3, at least partly if not totally. PRMT5 and its downstream effector FGFR3 may be potential targets for anticancer strategy.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Daoke
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Tiansong
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Qinchen
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
mesh_terms: D002277:Carcinoma; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011484:Protein-Arginine N-Methyltransferases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3