In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

Dam, Peter van; Dam, Pieter-Jan H.H. van; Rolfo, Christian; Giallombardo, Marco; Berckelaer, Christophe Van; Trinh, Xuan Bich; Altıntaş, Sevilay; Huizing, Manon; Papadimitriou, Κonstantina; Tjalma, Wiebren; Laere, Steven Van

doi:10.18632/oncotarget.6667

Cited by 22 publications

(24 citation statements)

References 44 publications

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“…From these probesets, six genes ( AURKA , DTL , HMGB3 , KIF2C , NEK2 , and RFC4 ) were overexpressed in CC cell lines compared to cancer samples, suggesting their potential role as biomarkers in CC early diagnosis. 53 One of these genes, such as RFC4 , was also identified in our study. Furthermore, our conclusion generated from both expression and survival analysis suggested that RFC4 might have a prognostic value.…”

Section: Discussionsupporting

confidence: 70%

Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy

Tang¹,

Xu²,

Lü³

et al. 2018

CMAR

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PurposeCervical cancer (CC) is one of the most common malignant tumors among women. The present study aimed at integrating two expression profile datasets to identify critical genes and potential drugs in CC.Materials and methodsExpression profiles, GSE7803 and GSE9750, were integrated using bioinformatics methods, including differentially expressed genes analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and protein–protein interaction (PPI) network construction. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis websites. Connectivity Map (CMap) was used to query potential drugs for CC.ResultsA total of 145 upregulated genes and 135 downregulated genes in CC were identified. The functional changes of these differentially expressed genes related to CC were mainly associated with cell cycle, DNA replication, p53 signaling pathway, and oocyte meiosis. A PPI network was identified by STRING with 220 nodes and 2,111 edges. Thirteen key genes were identified as the intersecting genes of the enrichment pathways and the top 20 nodes in PPI network. Survival analysis revealed that high mRNA expression of MCM2, PCNA, and RFC4 was significantly associated with longer overall survival, and the survival was significantly better in the low-expression RRM2 group. Moreover, CMap predicted nine small molecules as possible adjuvant drugs to treat CC.ConclusionOur study found key dysregulated genes involved in CC and potential drugs to combat it, which might provide insights into CC pathogenesis and might shed light on potential CC treatments.

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Section: Discussionsupporting

confidence: 70%

Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy

Tang¹,

Xu²,

Lü³

et al. 2018

CMAR

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“…Through direct stimulation, cell cycle genes synergize with E6/E7 oncoprotein-mediated blockade of cell cycle suppressors, p53 and RB, to promote cancer progression [ 40 ]. More recently, an in silico pathway analysis revealed that deregulation of the cell cycle is one of the major trademarks in cervical cancer [ 41 ]. In addition, this study also suggests that the major components of cell cycle pathway, such as CDK1/2, could be potential new targets for treating cervical cancer [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…More recently, an in silico pathway analysis revealed that deregulation of the cell cycle is one of the major trademarks in cervical cancer [ 41 ]. In addition, this study also suggests that the major components of cell cycle pathway, such as CDK1/2, could be potential new targets for treating cervical cancer [ 41 ]. However, this concept has not yet been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatics and in vitro experimental analyses identify the selective therapeutic potential of interferon gamma and apigenin against cervical squamous cell carcinoma and adenocarcinoma

et al. 2017

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The clinical management and treatment of cervical cancer, one of the most commonly diagnosed cancers and a leading cause of cancer-related female death, remains a huge challenge for researchers and health professionals. Cervical cancer can be categorized into two major subtypes: common squamous cell carcinoma (SCC) and adenocarcinoma (AC). Although it is a relatively rare histological subtype of cervical cancer, there has been a steady increase in the incidences of AC. Therefore, new strategies to treat cervical cancer are urgently needed. In this study, the potential uses of IFNγ-based therapy for cervical cancer were evaluated using bioinformatics approaches. Gene expression profiling identified that cell cycle dysregulation was a major hallmark of cervical cancer including SCC and AC subtypes, and was associated with poor clinical outcomes for cervical cancer patients. In silico and in vitro experimental analyses demonstrated that IFNγ treatment could reverse the cervical cancer hallmark and induce cell cycle arrest and apoptosis. Furthermore, we demonstrated that apigenin could enhance the anticancer activity of IFNγ in a HeLa cervical AC cell line by targeting cyclin-dependent kinase 1. Taken together, the present study suggests the selective therapeutic potential of IFNγ alone or in combination with apigenin for managing cervical SCC and AC.

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“…Further, sodium butyrate has been shown to influence the adhesion and growth-regulating galectin network that controls the proliferation of human colon cancer cells in vitro (10). DNA microarray analysis has contributed to our knowledge of tumour biomarkers and their potential suitability as targets of anticancer therapy as revealed by bioinformatics analyses (11)(12)(13).…”

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confidence: 99%

Antiproliferative Effects of Short-chain Fatty Acids on Human Colorectal Cancer Cells via Gene Expression Inhibition

Ohara

Mori

2019

Anticancer Res

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Background/Aim: Short-chain fatty acids (SCFAs) inhibit human colorectal cancer cell growth and tumorigenicity. We investigated the mechanism of the anti-proliferative effects of SCFAs on human colorectal cancer cells by examining their effects on gene expression. Materials and Methods: The DLD-1 cell line was cultured with different SCFAs. Gene groups whose expression levels decreased to <50% or increased >50% compared to untreated cells and the signalling pathways responsible for DLD-1 cell growth inhibition were identified and analyzed. Results: Genes whose expression levels decreased to ≤50% (791 genes) showed remarkable changes in gene function compared to genes whose expression levels increased ≥50%. These genes encode proteins involved in DNA replication and cell cycle/proliferation that contribute to major pathways responsible for suppression of colorectal carcinogenesis pathways. Conclusion: SCFAs inhibited the expression of genes encoding proteins involved in DNA replication and cell cycle/proliferation of human colorectal cancer cells and exerted antiproliferative activity via different pathways.

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In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

Cited by 22 publications

References 44 publications

Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy

Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy

Bioinformatics and in vitro experimental analyses identify the selective therapeutic potential of interferon gamma and apigenin against cervical squamous cell carcinoma and adenocarcinoma

Antiproliferative Effects of Short-chain Fatty Acids on Human Colorectal Cancer Cells via Gene Expression Inhibition

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