Screening of potentially crucial genes and regulatory factors involved in epithelial ovarian cancer using microarray analysis

Abstract

The present study aimed to screen potential genes implicated in epithelial ovarian cancer (EOC) and to further understand the molecular pathogenesis of EOC. In order to do this, datasets GSE14407 (containing 12 human ovarian cancer epithelia samples and 12 normal epithelia samples) and GSE29220 (containing 11 salivary transcriptomes from ovarian cancer patients with serous papillary adenocarcinoma and 11 matched controls) were obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) within these datasets were screened using the Linear Models for Microarray Data package, and potential gene functions were predicted by functional and pathway enrichment analyses. Additionally, module analysis of protein-protein interaction networks was performed using MCODE software in Cytoscape. The potential microRNAs (miRNAs/miRs) and transcription factors (TFs) regulating DEGs were also analyzed, and the integrated TF-DEG and miRNA-DEG regulatory networks were visualized with Cytoscape. In total, 31 upregulated DEGs and 64 downregulated DEGs were screened. The upregulated DEGs, such as centromere protein F (CENPF) and ubiquitin like with PHD and ring finger domains 1 (UHRF1), were significantly associated with the cell cycle and were regulated by the TF nuclear transcription factor Y (NF-Y). CENPF was modulated by miR-373, and UHRF1 was regulated by miR-146a. The downregulated DEGs, such as aldehyde dehydrogenase 1 family member A2 (ALDH1A2), were distinctly involved in the response to estrogen stimulus and modulated by tumor protein 53 (TP53); protocadherin 9 (PCDH9) was regulated by TP53, miR-92b-3p and miR-137. The DEGs, including CENPF, UHRF1, ALDH1A2 and PCDH9, and a set of gene regulators, including all NFY genes, TP53, miR-373, miR-146a, miR-92b-3p and miR-137, may be involved in the pathogenesis of EOC.

The Significance of MicroRNAs Expression in Regulation of Extracellular Matrix and Other Drug Resistant Genes in Drug Resistant Ovarian Cancer Cell Lines

“…PCDH9 (protocadherin 9), a member of the protocadherin protein family [97], is a calium-dependent adhesion protein playing a role in neural cell interaction [98]. It is a tumor suppressor gene with decreased expression in ovarian [99] and gastric cancer [100], and its downregulation usually correlates with disease progression and shorter survival. Previously, we observed the PCDH9 downregulation in three PAC resistant cell lines [92], suggesting its significance in resistance to this cytotoxic agent.…”

miR-92b-3p acts as a tumor suppressor by targeting Gabra3 in pancreatic cancer

“…It has been suggested that phosphorylated ΔNp63α can up-regulate miR-92b-3p in squamous cell carcinomas [ 35 ]. Another study of epithelial ovarian cancer revealed that miR-92b could be regulated by aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and protocadherin 9 (PCDH9) [ 36 ]. As with pancreatic cancer, the genes involved in regulating miR-92b remain unknown.…”

Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger-containing 1 (UHRF1) for anti-cancer drug development

“…UHRF1 is part of a six-gene signature for predicting a risk score that classifies non-small cell lung cancer (NSCLC) patients into either high or low-risk categories [ 55 ]. Microarray analysis of epithelial ovarian cancer (EOC) along with matched healthy controls has recently identified UHRF1 as one of the key differentially upregulated genes during disease pathogenesis [ 56 ]. The results highlighted that UHRF1 could act as a causative factor in ovarian cancer and as a suitable target for the development of anti-cancer therapies [ 57 ].…”