Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

Wang, Daguang; Chen, Guang; Wen, Xiaoyu; Wang, Dan; Cheng, Zhihua; Sun, Siqiao

doi:10.7314/apjcp.2015.16.4.1361

Cited by 14 publications

(7 citation statements)

References 39 publications

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“…NCAPG has been reported to be a mitotic gene, and its overexpression is responsible for the cell proliferation and migration in hepatocellular carcinoma [ 36 ]. Consistent with our study, NCAPG is differentially expressed in GC tissues compared to normal control tissues, and is enriched in the cell cycle term [ 37 ]. Therefore, we speculated that the downregulation of miR-193b-3p might contribute to GC cell proliferation by mediating the upregulation of NCAPG .…”

Section: Discussionsupporting

confidence: 91%

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

Song

et al. 2018

Biol Res

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BackgroundEmerging evidence indicate that miRNAs play an important role on gastric cancer (GC) progression via regulating several downstream targets, but it is still partially uncovered. This study aimed to explore the molecular mechanisms of GC by comprehensive analysis of mRNAs and miRNA expression profiles.MethodsThe mRNA and miRNA expression profiles of GSE79973 and GSE67354 downloaded from Gene Expression Omnibus were used to analyze the differentially expressed genes (DEGs) and DE-miRNAs among GC tissues and normal tissues. Then, targets genes of DE-miRNAs were predicted and the DE-miRNA–DEG regulatory network was constructed. Next, function enrichment analysis of the overlapped genes between the predicted DE-miRNAs targets and DEGs was performed and a protein–protein interactions network of overlapped genes was constructed. Finally, RT-PCR analysis was performed to detect the expression levels of several key DEGs and DE-miRNAs.ResultsA set of 703 upregulated and 600 downregulated DEGs, as well as 8 upregulated DE-miRNAs and 27 downregulated DE-miRNAs were identified in GC tissue. hsa-miR-193b-3p and hsa-miR-148a-3p, which targeted most DEGs, were highlighted in the DE-miRNA–DEG regulatory network, as well as hsa-miR-1179, which targeted KNL1, was newly predicted to be associated with GC. In addition, NCAPG, which is targeted by miR-193b-3p, and KNL1, which is targeted by hsa-miR-1179, had higher degrees in the PPI network. RT-qPCR results showed that hsa-miR-148a-3p, hsa-miR-193b-3p, and hsa-miR-1179 were downregulated, and NCAPG and KNL1 were upregulated in GC tissues; this is consistent with our bioinformatics-predicted results.ConclusionsThe downregulation of miR-193b-3p might contribute to GC cell proliferation by mediating the upregulation of NCAPG; as additionally, the downregulation of miR-193b-3p might contribute to the mitotic nuclear division of GC cells by mediating the upregulation of KNL1.

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Section: Discussionsupporting

confidence: 91%

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

Song

et al. 2018

Biol Res

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“… 13 – 15 , 19 – 24 , 35 In this report, CCNB1 and CCNB2 were upregulated in GC, which was consistent with previous studies. 35 , 52 – 54 The CCNB1 mRNA overexpression was also confirmed in different GC Lauren subtypes, which indicated that CCNB1 might be helpful to guide GC classification. Relevant research showed that overexpression of CCNB1 was associated with clinical stage, 54 lymph lode metastasis, 35 , 53 , 54 and poor survival in GC patients.…”

Section: Discussionmentioning

confidence: 83%

Clinical significance and biological roles of cyclins in gastric cancer

Zhang¹,

Li²,

Wang³

et al. 2018

OTT

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Background and aimCyclins have been reported to be overexpressed with poor prognosis in several human cancers. However, limited numbers of studies evaluated the expressions and prognostic roles of cyclins in gastric cancer (GC). We aim to evaluate the expressions and prognostic roles of cyclins. Also, further efforts were made to explore biological function of the differentially expressed cyclins.MethodsCyclins expressions were analyzed by Oncomine and The Cancer Genome Atlas datasets, and the prognostic roles of cyclins in GC patients were investigated by the Kaplan–Meier Plotter database. Then, a comprehensive PubMed literature search was performed to identify expression and prognosis of cyclins in GC. Biological functions of the differentially expressed cyclins were explored through Enrich R platform, and KEGG and transcription factor were analyzed.ResultsThe expression levels of CCNA2 (cyclin A2), CCNB1 (cyclin B1), CCNB2 (cyclin B2), and CCNE1 (cyclin E1) mRNAs were identified to be significantly higher in GC tissues than in normal tissues in both Oncomine and The Cancer Genome Atlas datasets. High expressions of CCNA2, CCNB1, and CCNB2 mRNAs were identified to be related with poor overall survival in Kaplan–Meier Plotter dataset. Evidence from clinical studies showed that CCNB1 was related with overall survival in GC patients. Cyclins were associated with several biological pathways, including cell cycle, p53 signaling pathway, FoxO signaling pathway, viral carcinogenesis, and AMPK signaling pathway. Enrichment analysis also showed that cyclins interacted with some certain transcription factors, such as FOXM1, SIN3A, NFYA, and E2F4.ConclusionBased on our results, high expressions of cyclins were related with poor prognosis in GC patients. The above information might be useful for better understanding the clinical and biological roles of cyclins mRNA and guiding individualized treatments for GC patients.

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“…High level of CCNB1 expression has been detected in a variety of cancers [22–26], including GC [27], resulting in uncontrolled cell growth. A recent study reported that cyclin B1 and cyclin B2 were the most significant candidate biomarkers in GC [28]. …”

Section: Discussionmentioning

confidence: 99%

ISL1, a novel regulator ofCCNB1,CCNB2andc-MYCgenes, promotes gastric cancer cell proliferation and tumor growth

et al. 2016

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Islet-1 (ISL1) belongs to the LIM homeodomain transcription factor family, which is specifically expressed in certain tissue types only. Previously, we reported that ISL1 is aberrantly overexpressed in gastric cancer (GC). However, its role in GC is not clear. Here, we report that ISL1 is aberrantly upregulated not only in human gastric carcinoma tissues but also in some GC cell lines. Upregulated ISL1 expression enhanced xenografted gastric carcinoma development, while ISL1 knockdown inhibited GC growth in nude mice. ISL1 overexpression promoted GC cell proliferation, colony formation, and cell growth in soft agar, and facilitated cell cycle transition in GC cells, demonstrated an increase in the proportion of cells in the G2/M and S phases and a decrease in the proportion of cells in the G1 phase. Furthermore, we provide evidence that ISL1 is a novel regulator of the cyclin B1 (CCNB1), cyclin B2 (CCNB2) and c-myc (c-MYC) genes. ISL1 activated the expression of these genes in GC cells by binding to the conserved binding sites on their promoters or enhancers. The expression levels of the genes were decreased in response to ISL1 knockdown. Therefore, ISL1 may serve as a potential therapeutic target in GC.

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Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

Cited by 14 publications

References 39 publications

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

Clinical significance and biological roles of cyclins in gastric cancer

ISL1, a novel regulator ofCCNB1,CCNB2andc-MYCgenes, promotes gastric cancer cell proliferation and tumor growth

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