Up-regulation of FN1, Activation of Maturation Promoting Factor and Associated Signaling Pathway Facilitates Epithelial-Mesenchymal Transition, Inhibits Apoptosis and Elevates Proliferation Rate of Breast Cancer Cells: In Silico Analysis of Microarray Datasets

Background: Knowing that the molecular mechanisms underlying breast cancer (BC) are not yet fully understood it was considered worth to launch investigation for the detection of key molecular pathways and associated genes and proteins. Methods: In total two microarray based datasets (GSE10810 and GSE29431), consisting of 89 breast cancer samples and 31 controls, were retrieved from the Gene Expression Omnibus (GEO) database and processed to identify the differentially expressed genes (DEGs). The pathway and functional enrichment analyses of DEGs were performed using DAVID online tool. Protein-Protein interaction (PPI) network was constructed using an online tool STRING and visualized through Cytoscape software to identify the significant module and hub genes via MCODE and Cytohubba applications. The identified hub genes were then further analyzed to document their response in Kaplan-Meier (KM) survival curve analysis, investigate differential expression profile and its correlation with promoter’s methylation status, and finally for the construction of the gene-drug interaction network. Results: In total 449 DEGs were detected including 151 up-regulated and 298 down-regulated genes. The identified DEGs were enriched in various cancer related biological functions and pathways. Based on PPI network analysis of the DEGs, six hub genes, CDK1, FN1, AURKA, CCNB2, BIRC5, and TOP2A, were correlated with worse overall survival (OS) of the breast cancer patients. Conclusion: The extensive in silico analysis has been helpful to evaluate evidence highlighting the prominent role played by the identified hub genes in stimulating breast tumor growth through the activation of Maturation Promoting Factor (MPF), PI3K/AKT signaling, and associated pathways that could be targeted for devising effective treatment strategies.

Cyclins regulating oocyte meiotic cell cycle progression†

Oocyte meiotic maturation is a vital and final process in oogenesis. Unlike somatic cells， the oocyte needs to undergo two continuous meiotic divisions (meiosis I and meiosis II) to become a haploid gamete. Notably, oocyte meiotic progression includes two rounds of unique meiotic arrest and resumption. The first arrest occurs at the G2 (germinal vesicle) stage and meiosis resumption is stimulated by a gonadotropin surge; the second arrest takes place at the metaphase II stage, the stage from which it is released when fertilization takes place. The maturation-promoting factor, which consists of cyclin B1 (CCNB1) and cyclin-dependent kinase 1 (CDK1), is responsible for regulating meiotic resumption and progression, while CDK1 is the unique CDK that acts as the catalytic subunit of maturation-promoting factor. Recent studies showed that except for cyclin B1, multiple cyclins interact with CDK1 to form complexes, which are involved in the regulation of meiotic progression at different stages. Here, we review and discuss the control of oocyte meiotic progression by cyclins A1, A2, B1, B2, B3, and O.

The potential roles of c-Jun N-terminal kinase (JNK) during the maturation and aging of oocytes produced by a marine protostome worm

SummaryPrevious investigations have indicated that c-Jun N-terminal kinase (JNK) regulates the maturation and aging of oocytes produced by deuterostome animals. In order to assess the roles of this kinase in a protostome, oocytes of the marine nemertean worm Cerebratulus were stimulated to mature and subsequently aged before being probed with phospho-specific antibodies against active forms of JNK and maturation-promoting factor (MPF). Based on blots of maturing oocytes, a 40-kD putative JNK is normally activated during germinal vesicle breakdown (GVBD), which begins at 30 min post-stimulation with seawater, whereas treating immature oocytes with JNK inhibitors downregulates both the 40-kD JNK signal and GVBD, collectively suggesting a 40-kD JNK may facilitate oocyte maturation. Along with this JNK activity, mature oocytes also exhibit high levels of MPF at 2 h post-stimulation. However, by ~6–8 h post-GVBD, mature oocytes lose the 40-kD JNK signal, and at ~20–30 h of aging, an ~48-kD phospho-JNK band arises as oocytes deactivate MPF and begin to lyse during a necroptotic-like mode of death. Accordingly, JNK inhibitors reduce the aging-related 48-kD JNK phosphorylation while maintaining MPF activity and retarding oocyte degradation. Such findings suggest that a 48-kD JNK may help deactivate MPF and trigger death. Possible mechanisms by which JNK activation either together with, or independently of, protein neosynthesis might stimulate oocyte degradation are discussed.