Dataset Information

Metastasis Suppressor NME1 Directly Activates Transcription of the ALDOC Gene in Melanoma Cells.

ABSTRACT: BACKGROUND/AIM:NME/NM23 nucleoside diphosphate kinase 1 (NME1) is a metastasis suppressor gene, exhibiting reduced expression in metastatic cancers and the ability to suppress metastatic activity of cancer cells. We previously identified NME1-regulated genes with prognostic value in human melanoma. This study was conducted in melanoma cell lines aiming to elucidate the mechanism through which NME regulates one of these genes, aldolase C (ALDOC). MATERIALS AND METHODS:ALDOC mRNA and protein expression was measured using qRT-PCR and immunoblot analyses. Promoter-luciferase constructs and chromatin immunoprecipitation were employed to measure the impact of NME1 on ALDOC transcription. RESULTS:NME1 enhanced ALDOC transcription, evidenced by increased expression of ALDOC pre-mRNA and activity of an ALDOC promoter-luciferase module. NME1 was detected at the ALDOC promoter, and forced NME1 expression resulted in enhanced occupancy of the promoter by NME1, increased presence of epigenetic activation markers (H3K4me3 and H3K27ac), and recruitment of RNA polymerase II. CONCLUSION:This is the first study to indicate that NME1 induces transcription through its direct binding to the promoter region of a target gene.

SUBMITTER: Pamidimukkala NV

PROVIDER: S-EPMC6367674 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Metastasis Suppressor NME1 Directly Activates Transcription of the <i>ALDOC</i> Gene in Melanoma Cells.

Pamidimukkala Nidhi V NV Leonard Mary Kathryn MK Snyder Devin D McCorkle Joseph R JR Kaetzel David M DM

Anticancer research 20181101 11

<h4>Background/aim</h4>NME/NM23 nucleoside diphosphate kinase 1 (NME1) is a metastasis suppressor gene, exhibiting reduced expression in metastatic cancers and the ability to suppress metastatic activity of cancer cells. We previously identified NME1-regulated genes with prognostic value in human melanoma. This study was conducted in melanoma cell lines aiming to elucidate the mechanism through which NME regulates one of these genes, aldolase C (ALDOC).<h4>Materials and methods</h4>ALDOC mRNA an ...[more]

PMID: 30396920

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Project description:NME1 is a well-documented metastasis suppressor gene, with suppressor activity demonstrated across a wide spectrum of human cancers including melanoma and carcinomas of the breast, stomach and thyroid. A primary aim of the current study was to identify profiles of genes whose expression is regulated by NME1 in cell lines of melanoma and thyroid carcinoma origin. Impact of NME1 was determined by forcing its expression transiently in cell lines using a novel Ad5-based adenoviral vector (Ad5-NME1), followed 48 h later by analysis of RNA expression profiles using the U133A microarray chip. Robust NME1 expression was achieved following infection with the Ad5-NME1 adenovirus in the human metastasis-derived cell lines WM1158 (melanoma) and WRO82 (follicular thyroid carcinoma), resulting in wide-ranging effects on gene expression in both settings. A substantial proportion of the NME1-regulated genes identified in the analyses were of clear potential relevance to metastasis, such as matrix metalloproteinase-1 (MMP1), angiopoietin-2 (ANGPT2), SERPINB9 and colony stimulating factor receptor-2B (CSFR2B). Nine genes were identified (false discovery rate <0.1) that were regulated by NME1 in both the WM1158 and WRO82 cell lines, each possessing one or more such metastasis-relevant activities as stress fiber formation and focal adhesion (PPM1E, ZYX, PFN1), chemotaxis (CCR1) epithelial-mesenchymal signaling (WNT6), differentiation and morphogenesis (TBX4, ZFP36L2), and G protein modulation (GPR52 and PFN1). In addition, a number of the NME1-regulated genes were shown to be of prognostic value for distant disease-free survival and overall survival in melanoma and breast cancer. The combined expression of three NME1-regulated genes CSFR2B, MSF4A1 and SERPINB9 provided a strongly synergistic correlation with distant disease-free survival in the basal subtype of breast cancer (p<3.5e(-5), hazard ratio=0.33). Our study demonstrates that analysis of NME1-dependent gene expression is a powerful approach for identifying potential modulators of metastatic potential in multiple cancer types, which in turn may represent useful therapeutic targets. The study also highlights NME1-dependent genes as potential prognostic/diagnostic indices, which are profoundly lacking at present in melanoma.

Dataset Information

Metastasis Suppressor NME1 Directly Activates Transcription of the ALDOC Gene in Melanoma Cells.

Publications

Metastasis Suppressor NME1 Directly Activates Transcription of the <i>ALDOC</i> Gene in Melanoma Cells.

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