A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis
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Lin Zhang1,*, Qin Huang1,*, Jiatao Lou2, Liangjian Zou3, Yiguo Wang4, Peng Zhang1, Guang Yang1, Junyi Zhang1, Lan Yu1, Dai Yan1, Chenyi Zhang1, Jing Qiao1, Shuting Wang1, Sai Wang1, Yongdong Xu5, Hongbin Ji1,7,8, Zhengjun Chen1,6,7, Zhe Zhang1,6
1Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China
2Shanghai Lung Tumor Clinical Medical Center, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
3Institute of Cardiothoracic Surgery, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai, China
4Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
5Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
6Cancer Research Center, Shanghai Xu-Hui Central Hospital, Shanghai Clinical Center, CAS, Shanghai, China
7School of Life Science and Technology, Shanghai Tech University, Shanghai, China
8CAS Center for Excellence in Molecular Cell Science, SIBCB, SIBS, CAS, Shanghai, China
*These authors have contributed equally to this work
Zhe Zhang, email: [email protected]
Zhengjun Chen, email: [email protected]
Keywords: PHF14, KIF4A, lung carcinogenesis, mitosis, biomarker
Received: April 12, 2016 Accepted: January 03, 2017 Published: February 01, 2017
The plant homeodomain (PHD) finger-containing proteins have been implicated in many human diseases including cancer. In this study, we found that PHF14, a newly identified PHD finger protein, is highly expressed in lung cancer. The high expression level of PHF14 was associated with adenocarcinoma and poor survival in lung cancer patients. Knocking down PHF14 suppressed cancer cell growth and carcinogenesis, while over-expressing PHF14 promoted cell proliferation. During cell division, PHF14 directly bound to and co-localized with KIF4A (a nuclear motor protein involved in lung carcinogenesis) to form a functional complex. Similarly to the effect of KIF4A depletion, silencing PHF14 in several cell lines caused cell mitotic defects, prolonged M phase, and inhibited cell proliferation. What’s more, these two proteins had a synergistic effect on cell proliferation and were significantly co-overexpressed in lung cancer tissues. Our data provide new insights into the biological significance of PHD finger proteins and imply that PHF14 may be a potential biomarker for lung cancer.
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