Over-expression of prolyl hydroxylase-1 blocks NF-κB-mediated cyclin D1 expression and proliferation in lung carcinoma cells

Xiao Xie; Haibo Xiao; Fangbao Ding; Hong Zhong; Jiaquan Zhu; Nan Ma; Ju Mei

doi:10.1016/j.cancergen.2014.04.008

Over-expression of prolyl hydroxylase-1 blocks NF-κB-mediated cyclin D1 expression and proliferation in lung carcinoma cells

Cancer Genet. 2014 May;207(5):188-94. doi: 10.1016/j.cancergen.2014.04.008. Epub 2014 May 4.

Authors

Xiao Xie¹, Haibo Xiao¹, Fangbao Ding¹, Hong Zhong¹, Jiaquan Zhu¹, Nan Ma¹, Ju Mei²

Affiliations

¹ Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
² Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China. Electronic address: ju_mei63@126.com.

PMID: 24935227
DOI: 10.1016/j.cancergen.2014.04.008

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.

Keywords: NF-κB; PHD1; cyclin D1; tumor growth.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids, Dicarboxylic / pharmacology
Animals
Cell Line, Tumor
Cell Proliferation
Cyclin D1 / biosynthesis*
Cyclin D1 / genetics
HEK293 Cells
Humans
Hypoxia-Inducible Factor-Proline Dioxygenases / antagonists & inhibitors
Hypoxia-Inducible Factor-Proline Dioxygenases / biosynthesis
Hypoxia-Inducible Factor-Proline Dioxygenases / genetics
Hypoxia-Inducible Factor-Proline Dioxygenases / metabolism*
Interleukin-1beta / biosynthesis
Interleukin-8 / biosynthesis
Lung Neoplasms / enzymology*
Lung Neoplasms / pathology*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
RNA Interference
RNA, Messenger / biosynthesis
S Phase Cell Cycle Checkpoints / genetics
Transcription Factor RelA / antagonists & inhibitors*
Transcription Factor RelA / genetics
Tumor Necrosis Factor-alpha / biosynthesis
Xenograft Model Antitumor Assays

Substances

Amino Acids, Dicarboxylic
CXCL8 protein, human
IL1B protein, human
Interleukin-1beta
Interleukin-8
RELA protein, human
RNA, Messenger
Transcription Factor RelA
Tumor Necrosis Factor-alpha
Cyclin D1
EGLN2 protein, human
Hypoxia-Inducible Factor-Proline Dioxygenases
oxalylglycine