Gene expression profiling analysis of the role of miR-22 in clear cell ovarian cancer

Abstract

This study aimed to investigate the role and potential mechanism of miR-22 in clear cell ovarian cancer (CCOC) progression. The gene expression profile of GSE16568, including 3 CCOC samples with miR-22 overexpression and 3 negative controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the limma package in R. Gene Ontology (GO) and pathway enrichment analysis of DEGs were performed by using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, protein-protein interaction (PPI) network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Besides, the miR-22 -mRNA interaction pairs were predicted to explore the critical genes involved in the cancer. Totally, 95 up-regulated DEGs and 51 down-regulated DEGs were identified. The DEGs were enriched in different GO terms and pathways. The up-regulated genes cyclin-dependent kinases (CDK6), MDM2 oncogene, E3 ubiquitin protein ligase (MDM2), and thrombospondin 1 (THBS1) were involved in the p53 signaling pathway. The up-regulated gene FBJ murine osteosarcoma viral oncogene homolog (FOS) was a hub protein in the PPI network of the DEGs. The down-regulated DEGs including lymphoid enhancer-binding factor 1 (LEF1) and v-myb avian myeloblastosis viral oncogene homolog (MYB) were mainly associated with immunity. Nine DEGs as target genes were identified to be recognized by miR-22. Our study suggested that several key genes such as CDK6, MDM2, LEF1, MYB, and FOS that involved in different pathways including p53 signaling pathway were associated with CCOC progression. miR-22 may play an essential role in cell migration and invasion in CCOC through targeting responsive genes.

miR-22-Notch Signaling Pathway Is Involved in the Regulation of the Apoptosis and Autophagy in Human Ovarian Cancer Cells

“…20) For instance, the lower miR-22 expressions are found in hundreds of clinical samples of the osteosarcoma, rhabdomyosarcoma, prostate, cervical and lung primary tumors. 8,12) miR-22 expression detected by RT-qPCR is significantly downexpressed in the osteosarcoma MG-63 cells 21) and tissues. 11) The expression of miR-22 in hepatocellular carcinoma (HCC) tissues and cell lines are much lower than that in normal control.…”

“…11) Furthermore, miR-22 contributes to cellular differentiation, migration and invasion by regulating its downstream transcription factors. 12,13) Notch pathway is an evolutionarily conserved signaling pathway which is activated to release the intracellular domain of Notch (NICD) to activate the Notch target genes Hes-1 and c-Myc. The Notch family consists of four receptors and five ligands.…”

Serum miR-22 as potential non-invasive predictor of poor clinical outcome in newly diagnosed, uniformly treated patients with diffuse large B-cell lymphoma: an explorative pilot study

“…In our study, we identified ten pathways significantly enriched with the miR-22 anticorrelated genes related to cell cycle, CDK6 and CDKN1A . CDK6 is a member of the CDK family, which comprises heteromeric serine/threonine kinases that control progression and regulate mammalian cell division through the cell cycle in collaboration with their regulatory subunits, the cyclins [ 61 , 62 ]. CDKN1A is a CDK inhibitor which physically interacts with, and inhibits, the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, preventing phosphorylation of critical cyclin-dependent kinase substrates thus functioning as a regulator of cell cycle progression during the G1 and S phases [ 63 ].…”

“…CDKN1A is a CDK inhibitor which physically interacts with, and inhibits, the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, preventing phosphorylation of critical cyclin-dependent kinase substrates thus functioning as a regulator of cell cycle progression during the G1 and S phases [ 63 ]. Interestingly, both CDK6 and CDKN1A are involved in p53 signaling pathway, suggesting that the p53–miR-22– CDK6 and/or CDKN1A axis could play a major regulatory role in the determination of p53-dependent apoptosis [ 61 , 64 , 65 ]. In particular, CDKN1A regulation by miR-22 has been shown to selectively determine the induction of p53-dependent apoptosis over cell cycle arrest acting as a molecular switch for the determination of p53-dependent cellular fate in response to various oncogenic stresses characterized by different damage intensity [ 65 ].…”