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A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

ABSTRACT: SPC24 is over-expressed in clinical lung adenocarcinoma samples, and high level of SPC24 is associated with advanced stages of lung tumors. Knocking down SPC24 repressed cell growth and promoted apoptosis. SPC24 deficiency reduced cancer cell migration as well. E-cadherin, one of the epithelial-mesenchymal transition markers, was up-regulated in the knockdown cells, along with down-regulation of N-cadherin and Vimentin. Oncomine expression analyses further confirmed that high level of SPC24 is associated with tumors from smokers, recurrent patients, or patients with shorter survivals.To reveal the role of SPC24, an important component of kinetochore, in the tumorigenesis of lung cancer, we performed Oncomine and immunohistochemistry (IHC) analyses for SPC24 in human lung adenocarcinoma tumors. We knocked down SPC24 in two non-small cell lung cancer (NSCLC) cell lines, PC9 and A549, by siRNA and evaluated cell proliferation, apoptosis, and migration in the SPC24-deficient cells. Using a mouse xenograft model, we compared in vivo tumor growth of the knockdown and control cells. We further performed multiple Oncomine expression analyses for SPC24 in various lung cancer datasets with important clinical characteristics and risk factors, including survival, recurrence, and smoking status.SPC24 is a novel oncogene of lung cancer, and can serve as a promising prognostic biomarker to differentiate lung tumors that have various clinicopathological characteristics. The findings of the current study will benefit the diagnosis, management, and targeted therapy of lung cancer.

SUBMITTER: Zhou J

PROVIDER: S-EPMC5630346 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

Zhou Juan J Yu Yang Y Pei Yunfeng Y Cao Chunping C Ding Chen C Wang Duping D Sun Li L Niu Guoping G

Oncotarget 20170704 39

<h4>Results</h4>SPC24 is over-expressed in clinical lung adenocarcinoma samples, and high level of <i>SPC24</i> is associated with advanced stages of lung tumors. Knocking down SPC24 repressed cell growth and promoted apoptosis. SPC24 deficiency reduced cancer cell migration as well. E-cadherin, one of the epithelial-mesenchymal transition markers, was up-regulated in the knockdown cells, along with down-regulation of N-cadherin and Vimentin. Oncomine expression analyses further confirmed that h ...[more]

PMID: 29029446

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Project description:Glucosamine‑phosphate N‑acetyltransferase 1 (GNPNAT1) is a member of the acetyltransferase superfamily, related to general control non‑depressible 5 (GCN5). It has been documented that GNPNAT1 expression is increased in lung cancer, whereas its involvement in breast cancer (BC) remains to be further investigated. The present study aimed to evaluate the expression levels of GNPNAT1 in BC and its effect on BC stem cells (BCSCs). The Cancer Genome Atlas (TCGA) database was used for the analysis of the expression of GNPNAT1 and its clinical significance. Cox regression and logistic regression analyses were used to evaluate prognosis‑related factors. The GNPNAT1‑binding protein network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) application. The biological signaling pathways implicated in GNPNAT1 were investigated through function enrichment analysis including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. The single‑sample GSEA method was used to investigate the connection between the level of immune infiltration and GNPNAT1 expression in BC. GNPNAT1 expression was upregulated in patients with BC and was significantly associated with a poor prognosis. GNPNAT1 and its co‑expressed genes were mostly enriched in nuclear transport, Golgi vesicle transport, ubiquitin‑like protein transferase activity and ribonucleoprotein complex binding, as determined using functional enrichment analysis. GNPNAT1 expression was positively associated with Th2 cells and T‑helper cells, and negatively associated with plasmacytoid dendritic cells, CD8+ T‑cells and cytotoxic cells. Additionally, the GNPNAT1 expression levels were considerably increased in BCSCs. GNPNAT1 knockdown markedly decreased the stemness ability of SKBR3 and Hs578T cells, including the production of CSC markers and mammosphere or clone formation, while GNPNAT1 overexpression increased the stemness level. Hence, the findings of the present study demonstrate that GNPNAT1 may be exploited as a novel prognostic biomarker and therapeutic target for BC.

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A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

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A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

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