title: Over-expression of prolyl hydroxylase-1 blocks NF-κB-mediated cyclin D1 expression and proliferation in lung carcinoma cells.
abstract: Prolyl hydroxylase-1 (PHD1), a member of the hypoxia inducible factor (HIF)-PHD family, plays an important role in regulating the stability of HIFs. The nuclear factor-κB (NF-κB) pathway consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. In this study, we demonstrate that PHD1 can inhibit NF-κB activity and its target genes in lung cancer cells based on both over-expression and RNA interference-mediated knockdown of PHD1 in human A549 lung cancer cells and HEK293 T cells. Of medical importance, PHD1 could induce cell cycle arrest in lung cancer cells, resulting in the suppression of cell proliferation. Xenograft tumor growth assays indicate that PHD1 plays a critical role in suppressing lung cancer growth. These findings reveal a new role of PHD1 in lung cancer and provide new treatment perspectives for cancer therapy by characterizing PHD1 as a potential target.
authors.affiliation: Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xie
authors.affiliation: Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Fangbao
authors.initials: F
authors.lastname: Ding
authors.affiliation: Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Jiaquan
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China. Electronic address: ju_mei63@126.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000600:Amino Acids, Dicarboxylic; C508606:CXCL8 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; C498143:RELA protein, human; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1; C447780:EGLN2 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; C040947:oxalylglycine
keywords: NF-κB; PHD1; cyclin D1; tumor growth