Dataset Information

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.

SUBMITTER: Mao X

PROVIDER: S-EPMC5325404 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NKAIN2 functions as a novel tumor suppressor in prostate cancer.

Mao Xueying X Luo Fei F Boyd Lara K LK Zhou Bowei B Zhang Yanling Y Stankiewicz Elzbieta E Marzec Jacek J Vasiljevic Natasa N Yu Yongwei Y Feng Ninghan N Xu Jia J Lorincz Attila A Jiang Yong Y Chelala Claude C Ren Guoping G Berney Daniel M DM Zhao Shan-Chao SC Lu Yong-Jie YJ

Oncotarget 20160901 39

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 i ...[more]

PMID: 27588475

Similar Datasets

Project description:Localized in the mitochondria, SIRT4 is a nicotinamide adenine dinucleotide (NAD +) -dependent adenosine diphosphate (ADP) -ribosyltransferase and is one of the least characterized members of the sirtuin family. Although it is well known that it shows deacetylase activity for energy metabolism, little is understood about its function in tumorigenesis. Recent research suggests that SIRT4 may work as both a tumor suppressor gene and an oncogene. However, the clinical significance of SIRT4 in prostate cancer remains unknown. In this study, we evaluated SIRT4 protein levels in cancerous prostate tissue and corresponding non-tumor prostate tissue via immunohistochemical staining on a tissue microarray including tissues from 89 prostate cancer patients. The association between SIRT4 expression and Gleason score was also determined. Further, shSIRT4 or stable prostate cancer cell lines (22RV1) overexpressing SIRT4 were constructed via lentiviral infection. Using Cell-Counting Kit-8 (CCK-8) assay, wound healing assay, migration, and invasion and apoptosis assays, the effects of SIRT4 on the migration, invasion ability, and proliferation of prostate cancer cells were investigated. We also determined the effect of SIRT4 on glutamine metabolism in 22RV1 cells. We found the protein levels of SIRT4 in prostate cancer tissues were significantly lower than those in their non-neoplastic tissue counterparts (P < 0.01); a lower SIRT4 level was also significantly associated with a higher Gleason score (P < 0.01). SIRT4 suppressed the migration, invasion capabilities, and proliferation of prostate cancer cells and induced cellular apoptosis. Furthermore, the invasion and migration of 22RV1 cells were mechanistically inhibited by SIRT4 via glutamine metabolism inhibition. In conclusion, the present study's findings showed that SIRT4 protein levels are significantly associated with the Gleason score in patients with prostate cancer, and SIRT4 exerts a tumor-suppressive effect on prostate cancer cells by inhibiting glutamine metabolism. Thus, SIRT4 may serve as a potential novel therapeutic target for prostate cancer.

Dataset Information

NKAIN2 functions as a novel tumor suppressor in prostate cancer.

Publications

NKAIN2 functions as a novel tumor suppressor in prostate cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets