title: Lower expression of Nrdp1 in human glioma contributes tumor progression by reducing apoptosis.
abstract: Ubiquitin ligase Nrdp1 (neuregulin receptor degradation protein 1) plays important roles in multiple physiological process because it can ubiquitinate various substrates such as ErbB3, BRUCE, MyD88, C/EBPβ, and Parkin, and so forth. In addition to the physiological function, it was also found to be involved in tumor progression. It has been shown that loss of Nrdp1 enhances breast cancer cell growth. Up to now, the role of Nrdp1 in glioma has not been elucidated. Here, we reported that Nrdp1 as well as cleaved caspase 3 was lower expressed in human glioma tissues comparing with the nontumorous. And then we found that the expression of Nrdp1 and cleaved caspase 3 was increased in the treatment of Temozolomide (TMZ), a drug for glioma chemotherapy. Further investigation indicated that transient transfection of Nrdp1 significantly promoted cell apoptosis by aggravating the degradation of BRUCE and activation of caspase 3. In addition, overexpression of Nrdp1 augmented TMZ induced apoptosis by evaluating the degradation of BRUCE and the activation of caspase 3, while silencing of Nrdp1 reduced the sensitivity to the TMZ by inhibiting the degradation of BRUCE and the activation of caspase 3 in human glioma cells. These observations show that Nrdp1 is a pro-apoptotic protein in human glioma and lower expression of Nrdp1 in human glioma may promote tumor progression by reducing apoptosis, suggesting that Nrdp1 may be an important regulator in the development of human glioma.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China; Department of Clinical Medicine, The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.forename: Jin
authors.initials: J
authors.lastname: Du
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Bao
authors.initials: B
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D000077204:Temozolomide; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018906:Antineoplastic Agents, Alkylating; C401541:BIRC6 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D025801:Ubiquitin; D003606:Dacarbazine; C452580:RNF41 protein, human; D044767:Ubiquitin-Protein Ligases; D053148:Caspase 3; D000077204:Temozolomide
keywords: BRUCE; Nrdp1; apoptosis; caspase 3; glioma