title: NKAIN2 functions as a novel tumor suppressor in prostate cancer.
abstract: Recurrent chromosome breakpoints at 6q22.31, leading to truncation and potential loss-of-function of the NKAIN2 gene, in Chinese prostate cancer patients were previously identified. In this study we investigated genomic, methylation and expression changes of NKAIN2 in a large number of prostate cancer samples and determined its functional role in prostate cancer cells. Fluorescence in situ hybridization analysis confirmed that NKAIN2 truncation is specific to Chinese while deletion of the gene is frequent in both Chinese and UK prostate cancers. Significantly reduced expression of NKAIN2 was also detected at both RNA and protein levels. Somatic mutations of NKAIN2 in prostate cancer samples exist but at very low frequency, suggesting that it is a putative tumor suppressor gene (TSG) with haploid insufficiency. Our functional studies showed that overexpression of NKAIN2 in prostate cancer cells inhibits cellular growth by promoting cell apoptosis, and decreasing cell migration and invasion. Conversely, knockdown of NKAIN2 promotes prostate cancer cell growth by inhibiting cell apoptosis, and increasing cell migration and invasion. These data imply that NKAIN2 is a novel TSG whose activity is commonly reduced in prostate cancer. It may restrain the disease development and progression by inducing apoptosis and suppressing cancer cell growth, migration and invasion. This study provides new insights into prostate carcinogenesis and opportunities for development of novel therapies for prostate cancer.
authors: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Xueying
authors: X
authors: Mao
authors: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University, Guangzhou, 510515, China.
authors: Fei
authors: F
authors: Luo
authors: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Lara K
authors: LK
authors: Boyd
authors: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University, Guangzhou, 510515, China.
authors: Bowei
authors: B
authors: Zhou
authors: Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, 310009, China.|Department of Gynecology and Obstetrics, Sir Run Run Shaw Hospital, Zhejiang University Medical College, Hangzhou, 310009, China.
authors: Yanling
authors: Y
authors: Zhang
authors: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Elzbieta
authors: E
authors: Stankiewicz
authors: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Jacek
authors: J
authors: Marzec
authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Natasa
authors: N
authors: Vasiljevic
authors: Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China.
authors: Yongwei
authors: Y
authors: Yu
authors: Department of Urology, Wuxi Second People's Hospital, Nanjing Medical University, Wuxi, 214002, China.
authors: Ninghan
authors: N
authors: Feng
authors: Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University, Guangzhou, 510515, China.
authors: Jia
authors: J
authors: Xu
authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Attila
authors: A
authors: Lorincz
authors: Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University, Guangzhou, 510515, China.
authors: Yong
authors: Y
authors: Jiang
authors: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Claude
authors: C
authors: Chelala
authors: Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, 310009, China.
authors: Guoping
authors: G
authors: Ren
authors: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Daniel M
authors: DM
authors: Berney
authors: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors: Shan-Chao
authors: SC
authors: Zhao
authors: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
authors: Yong-Jie
authors: YJ
authors: Lu
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D023281:Genomics; D006238:Haploidy; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C460140:NKAIN2 protein, human; D034741:RNA, Small Interfering
keywords: NKAIN2; chromosomal deletion and truncation; population difference; prostate cancer; tumor suppressor