Abstract
Background The rate of ovarian cancer (OC) is one of the highest in women's reproductive systems. An improperly expressed microRNA (miRNA) has been discovered to have a vital role in the pathophysiology of OC. However, more research into OC's miRNA-message RNA (mRNA) gene interaction network is required. Methods Firstly, the microarray data sets GSE25405 and GSE119055 from the GEO (Gene Expression Omnibus) database were downloaded and then analyzed with the GEO2R tool aiming at identifying DEMs (differential expressed miRNAs) between ovarian malignant tissue and ovarian normal tissue. The whole consistently changed miRNAs were then screened out to be candidate DEMs. For estimating underlying upstream transcription factors, FunRich was employed. miRNet was utilized to determine putative DEMs' downstream target genes. The R program was then used to do the GO annotation as well as the analysis of KEGG pathway enrichment for target genes. The PPI (protein-protein interaction), as well as the DEM-hub gene networks, were created by the Cytoscape software and STRING database. Finally, we chose the GSE74448 dataset to test the precision of hub gene expressions. Results We have screened out six (five upregulated and one downregulated) DEMs. The majority of upregulated and downregulated DEMs are likely regulated by SP1 (specificity protein 1). SP4 (s protein 4), POU2F1 (POU class 2 homeobox 1), MEF2A (myocyte-specific enhancer factor 2A), ARID3A (AT-rich interaction domain 3A), and EGR1 (early growth response 1) can regulate upregulated and downregulated DEMs. We have found 807 target genes (656 upregulated and 151 downregulated DEM), being generally enriched in focal adhesion and proteoglycans in cancer, gastric cancer, hepatocellular carcinoma, as well as breast cancer. The majority of hub genes are projected to be controlled by hsa-miR-429, hsa-miR-140-5p, hsa-miR-199a-5p, and hsa-miR-199a-3p after the DEM-hub gene network was built. VEGFA (vascular endothelial growth factor A), EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and HIF1A (hypoxia inducible factor 1 subunit alpha) expressions are consistent with the GSE74448 dataset in the first 18 hub genes. Conclusion We have built an underlying miRNA-mRNA interacting network in OC, giving us unparalleled insight into the disease's diagnosis and treatment.
Highlights
ovarian cancer (OC) is a malignancy in the female reproductive system, which is prevalent in patients over the age of 50
In 2009, a randomized clinical trial in China showed that the routine surveillance of OC using the carbohydrate antigen 125 (CA125) assay will increase the usage of chemotherapy, reduce the living quality of patients, and can’t improve the survival rate of patients [2]. e diagnosis of OC is so difficult as symptoms, medical history, and tests are usually not specific for OC
Five upregulated DEMs and one downregulated DEM are constantly changing in the two data sets and have been identified as the candidate DEMs for further analysis. Both strands (-5p and -3p) of has-miR-455 target the same genes to regulate articular cartilage homeostasis, with underlying treatment value for osteoarthritis (OA), are upregulated by Sox9 (SRY-box transcription factor 9), a crucial transcription factor of cartilage differentiation and function [19]. has-miR-199a-5p is the key regulator of the abnormal α1-antitrypsin (AAT)-deficient monocyte unfolded protein response, which can be regulated by epigenetic silencing in chronic obstructive pulmonary disease [20]. has-miR-1405p is an underlying prognostic factor for gastric cancer patients, being capable of mediating YES1 (YES proto-oncogene 1 and Src family tyrosine kinase) suppression [21]
Summary
OC is a malignancy in the female reproductive system, which is prevalent in patients over the age of 50. CA125 is less reliable in the diagnosis and not capable of screening early ovarian cancer. Journal of Oncology miRNA, whose size is approximately 22 nucleotides, belongs to the group of small ncRNAs (noncoding RNAs) It regulates one-third of the genomes and downregulates the expression level of its target gene at the posttranscriptional stage as an antisense RNA. MiRNA has been linked to a variety of human disorders, and it is thought to be the underlying target for cancer and other diseases detection and treatment [3]. Serum miRNA profiles are a potential and highly reliable biomarker for early detection and diagnosis of OC which has been proven in recent research [4]. We set out to discover particular targets for the diagnosis and treatment of OC by establishing an underlying miRNA-mRNA regulation network in the disease
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