A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis
| Autor: | Lan Yu, Junyi Zhang, Shuting Wang, Zhengjun Chen, Lin Zhang, Yiguo Wang, Jia-Tao Lou, Jing Qiao, Hongbin Ji, Guang Yang, Dai Yan, Chenyi Zhang, Liangjian Zou, Qin Huang, Sai Wang, Yongdong Xu, Peng Zhang, Zhe Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Gerontology Male Lung Neoplasms Kinesins Apoptosis medicine.disease_cause Mice 0302 clinical medicine Carcinoma Non-Small-Cell Lung Tumor Cells Cultured lung carcinogenesis Mice Inbred BALB C Middle Aged Prognosis Gene Expression Regulation Neoplastic Survival Rate Cell Transformation Neoplastic 030220 oncology & carcinogenesis Adenocarcinoma biomarker Female Research Paper medicine.medical_specialty Mice Nude Mitosis 03 medical and health sciences Internal medicine medicine Biomarkers Tumor Animals Humans Lung cancer Cell Proliferation Neoplasm Staging business.industry Cell growth Cancer medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology Cancer cell KIF4A business Carcinogenesis Follow-Up Studies Transcription Factors PHF14 |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Lin Zhang 1, * , Qin Huang 1, * , Jiatao Lou 2 , Liangjian Zou 3 , Yiguo Wang 4 , Peng Zhang 1 , Guang Yang 1 , Junyi Zhang 1 , Lan Yu 1 , Dai Yan 1 , Chenyi Zhang 1 , Jing Qiao 1 , Shuting Wang 1 , Sai Wang 1 , Yongdong Xu 5 , Hongbin Ji 1, 7, 8 , Zhengjun Chen 1, 6, 7 , Zhe Zhang 1, 6 1 Key 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 2 Shanghai Lung Tumor Clinical Medical Center, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China 3 Institute of Cardiothoracic Surgery, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai, China 4 Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China 5 Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China 6 Cancer Research Center, Shanghai Xu-Hui Central Hospital, Shanghai Clinical Center, CAS, Shanghai, China 7 School of Life Science and Technology, Shanghai Tech University, Shanghai, China 8 CAS Center for Excellence in Molecular Cell Science, SIBCB, SIBS, CAS, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhe Zhang, email: zhangzhe@sibcb.ac.cn Zhengjun Chen, email: zjchen@sibcb.ac.cn Keywords: PHF14, KIF4A, lung carcinogenesis, mitosis, biomarker Received: April 12, 2016 Accepted: January 03, 2017 Published: February 01, 2017 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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