title: RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway.
abstract: Ring finger protein 135 (RNF135), located on chromosome 17q11.2, is a RING finger domain-containing E3 ubiquitin ligase that was identified as a bio-marker and therapy target of glioblastoma. In our study, we confirmed that RNF135 was up-regulated in glioblastoma tissues compared with normal brain (NB) tissues, and that RNF135 knockdown inhibited proliferation and migration and led to cell cycle arrest in the G0/G1 phase in vivo. By lowering RNF135 expression, phosphorylated Erk and cell cycle protein CDK4 were down-regulated, while p27(Kip1) and p21(Waf1/Cip1) were up-regulated in U87 and U251 cells in vitro. In addition, using the immunofluorescence double labelling method, we found that RNF135 and P-Erk were co-localized in the cytoplasm and were highly expressed in glioblastoma samples compared with NB tissues. Moreover, the growth of U87 cell-transplanted tumours in nude mice was inhibited while transduced with Lv-shRNF135. Taken together, our findings demonstrate the biological effects of RNF135 in glioblastoma cell proliferation, migration and cell cycle, and its role in the progression of glioblastoma may be associated with the ERK signal transduction pathway.
authors: Department of Interventional therapy, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Yongjian
authors: Y
authors: Liu
authors: Department of Interventional therapy, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Feng
authors: F
authors: Wang
authors: Department of Interventional therapy, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Yongsheng
authors: Y
authors: Liu
authors: Department of Neurosurgery, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Yiqun
authors: Y
authors: Yao
authors: Department of Neurosurgery, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Xiupeng
authors: X
authors: Lv
authors: Department of Neurosurgery, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Bin
authors: B
authors: Dong
authors: Department of Neurosurgery, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Jun
authors: J
authors: Li
authors: Department of Neurosurgery, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Siyang
authors: S
authors: Ren
authors: Department of Neurosurgery, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Yiwen
authors: Y
authors: Yao
authors: Department of Neurosurgery, First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
authors: Yinghui
authors: Y
authors: Xu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; C522809:RNF135 protein, human; D044767:Ubiquitin-Protein Ligases; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4