title: Involvement of bleomycin hydrolase and poly(ADP-ribose) polymerase-1 in Ubc9-mediated resistance to chemotherapy agents.
abstract: Ubiquitin-conjugating protein 9 (Ubc9), the sole enzyme for sumoylation, plays critical roles in many physiological functions, such as DNA damage repair and genome integrity. Its overexpression led to poor prognosis and drug resistance in tumor chemotherapy. However, the underlying mechanism by which Ubc9 promotes tumor progress and influences the susceptibility to antitumor agents remains elusive. In this study, we used nine antitumor agents with distinct actions to explore Ubc9-mediated resistance in human breast carcinoma MCF-7 cells. Increase of susceptibility, respectively, to boningmycin, hydroxycamptothecine, cis-dichlorodiamineplatinum, 5-fluorouracil, vepeside and gemcitabine, but not for doxorubicin, vincristine and norcantharidin, was observed after the knockdown of Ubc9 protein level with RNA interference. Reduction of bleomycin hydrolase and poly(ADP-ribose) polymerase-1 levels after knockdown of Ubc9 suggests their contribution to Ubc9-mediated drug resistance. This is the first report on the sensitivity to hydroxycamptothecine, cis-dichlorodiamineplatinum and gemcitabine that increased after knockdown of bleomycin hydrolase at protein level. In conclusion, Ubc9 plays different roles of action in antitumor agents in chemotherapy. The process requires bleomycin hydrolase and poly(ADP-ribose) polymerase-1. The results are beneficial to deeply understanding of Ubc9 functions and for precise prediction of chemotherapy outcomes in tumors.
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P.R. China.
authors.forename: Huixian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P.R. China.
authors.forename: Qiyang
authors.initials: Q
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage / Q000031:analogs & derivatives; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004659:Enbucrilate / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000096:biosynthesis / Q000235:genetics*; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*; D014750:Vincristine / Q000008:administration & dosage; D000093542:Gemcitabine; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D025801:Ubiquitin; C555678:boningmycin; C493949:hydroxycamptothecin polybutylcyanoacrylate; D003841:Deoxycytidine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; C069741:norcantharidin; D044763:Ubiquitin-Conjugating Enzymes; D000071137:Poly (ADP-Ribose) Polymerase-1; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D004659:Enbucrilate; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine