Dataset Information

[Expression of nicotinamide-N-methyltransferase in gastric cancer and its biological and clinicopathological significance].

ABSTRACT:

Objective

To investigate the expression of nicotinamide-N-methyltransferase (NNMT) in gastric cancer (GC) and explore its biological and clinicopathological significance.

Objective

We screened the candidate genes associated with the classification and prognosis of gastric cancer by analyzing GEO, Oncomine and TCGA datasets. The molecular pathways and protein interaction network involving these candidate genes were analyzed using STRING, GSEA, David and Cytoscape software. The expressions of the candidate genes in 28 pairs of gastric cancer and adjacent tissues were detected with qRTPCR, and CCK-8 assay, clone formation assay, wound healing assay and Transwell assay were carried out to analyze the effects of modulation of NNMT expression on proliferation, invasion and migration of different gastric cancer cell lines.

Objective

NNMT was highly expressed in gastric cancer tissues and was negatively correlated with the prognosis of patients with gastric cancer. Pathway analysis showed that the high expression of NNMT was associated with adhesion-related pathway molecules such as extracellular matrix receptors, cell adhesion molecules, and cytokine receptors, while its low expression was associated with base mismatch repair and riboflavin metabolism. Protein interaction analysis showed that NNMT interacted with 16 differentially expressed proteins such as AURKA and was co-expressed with TAGLN, PTRF, AKAP12 and IGF2BP2. In clinical tissue specimens, qRT-PCR results showed that the expression of NNMT mRNA was significantly higher in gastric cancer tissues than in the adjacent tissues (P < 0.05). In gastric cancer cell lines, overexpression of NNMT was found to significantly promote cell proliferation, invasion and migration, while NNMT knockdown produced obvious inhibitory effects on cell proliferation, invasion and migration.

Objective

NNMT is highly expressed in gastric cancer and negatively correlated with the prognosis of gastric cancer patients. The high expression of NNMT promotes the proliferation, invasion and metastasis of gastric cancer cells, suggesting the potential of NNMT as prognostic marker of gastric cancer.

SUBMITTER: Wen Z

PROVIDER: S-EPMC8267982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Accumulating evidence indicates that numerous microRNAs are involved in the tumorigenesis and progression of gastric cancer, while the clinical significance of microRNA-214 in gastric cancer is poorly understood and the exact role of microRNA-214 in gastric cancer remains obscure. In the present study, expression levels of microRNA-214 in 80 gastric carcinoma tissues, 18 nontumourous gastric tissues, and 4 types of gastric cancer cell lines were quantified by reverse transcription followed by real-time quantitative polymerase chain reaction (RT-qPCR), and the relationship between microRNA-214 expression and cliniopathological characteristics including prognosis was explored. To investigate the potential role of microRNA-214 in gastric cancer cell biological behaviour, we performed cell proliferation, apoptosis, migration and invasion assays in four gastric cancer cell lines and an immortalized gastric cell line in vitro. Our results showed that microRNA-214 was dramatically downregulated in gastric cancer tissues and gastric cancer cell lines, compared with nontumourous gastric tissues. Stepwise downregulation of microRNA-214 expression was observed among nontumourous gastric mucosa, nonmetastasis gastric cancer tissues, and metastasis gastric cancer tissues. The expression of microRNA-214 was significantly inversely correlated with lymph node metastasis and tumour size but had no correlation with the patient's prognosis. Ectopic expression of microRNA-214 could inhibit cell migration and invasion ability in SGC7901 and MKN45 gastric cancer cells. And knockdown of microRNA-214 significantly facilitated cell proliferation, migration and invasion in a cell-specific manner in MKN28, BGC823 and GES-1 cells. Colony stimulating factor 1 (CSF1) was identified as a target gene of microRNA-214. In summary, our data demonstrated that microRNA-214 is a promising novel biomarker for lymph node metastasis in patients with gastric cancer. And we identified that downregulation of microRNA-214 may regulate the proliferation, invasion and migration of gastric cancer cells by directly targeting CSF1.

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[Expression of nicotinamide-N-methyltransferase in gastric cancer and its biological and clinicopathological significance].

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