Ovarian cancer is one of the most common malignant tumor of female genital organs which ranks the third morbidity. We aimed to provide a better understanding of the mechanism of invasion and metastasis of ovarian cancer. The ovarian cancer samples were downloaded from GEO. Then clustering was performed to classify the stage of miRNAs based on the difference of prognosis and metastasis. Furthermore, the miRNAs model was build and the survival analysis processes was performed to observe the influence on prognosis, invasion and metastasis. At last, miRNAs co-expression network was built to explore the core miRNAs and the risk classification model was built to perform the risk assessment based on these core miRNAs. A total of 17 significantly differential expressed miRNAs were obtained. Functional enrichment of 1,488 target genes, pathways like cell cycle, focal adhesion, and pathways in cancer, which are closely related to the proliferation and metastasis of cancer cells were highly enriched, this indicate that these miRNAs are related to the proliferation and metastasis of cancer cells. The co-expressed network shows that the high expression of hsa-miR-320 indicated negative prognosis and high risk of metastasis. In conclusion, the expression level of hsa-miR-320 is highly related to the migration and invasion of cancer. The high expression of hsa-miR-320 directly indicated negative prognosis and high risk of metastasis. These findings reveal that hsa-miR-320 may serve as an important therapeutic target in ovarian cancer therapy. J. Cell. Biochem. 118: 3654-3661, 2017. © 2017 Wiley Periodicals, Inc.
Background This study aimed to identify the hub genes associated with prognosis of patients with ovarian cancer by using integrated bioinformatics analysis and experimental validation. Methods Four microarray datasets (GSE12470, GSE14407, GSE18521 and GSE46169) were analyzed by the GEO2R tool to screen common differentially expressed genes (DEGs). Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, the (KEGG) pathway and Reactome pathway enrichment analysis, protein–protein interaction (PPI) construction, and the identification of hub genes were performed. Furthermore, we performed the survival and expression analysis of the hub genes. In vitro functional assays were performed to assess the effects of hub genes on ovarian cancer cell proliferation, caspase-3/7 activity and invasion. Results A total of 89 common DEGs were identified among these four datasets. The KEGG and Reactome pathway results showed that the DEGs were mainly associated with cell cycle, mitotic and p53 signaling pathway. A total of 20 hub genes were identified from the PPI network by using sub-module analysis. The survival analysis revealed that high expression of six hub genes ( AURKA, BUB1B, CENPF, KIF11, KIF23 and TOP2A ) were significantly correlated with shorter overall survival and progression-free survival of patients with ovarian cancer. Furthermore, the expression of the six hub genes were validated by the GEPIA database and Human Protein Atlas, and functional studies revealed that knockdown of KIF11 and KIF23 suppressed the SKOV3 cell proliferation, increased caspase-3/7 activity and attenuated invasive potentials of SKOV3 cells. In addition, knockdown of KIF11 and KIF23 up-regulated E-cadherin mRNA expression but down-regulated N-cadherin and vimentin mRNA expression in SKOV3 cells. Conclusion Our results showed that six hub genes were up-regulated in ovarian cancer tissues and may predict poor prognosis of patients with ovarian cancer. KIF11 and KIF23 may play oncogenic roles in ovarian cancer cell progression via promoting ovarian cancer cell proliferation and invasion.
Purpose: To explore miRNA-875-5p and epidermal growth factor receptor (EGFR) activities in tissues or cells from cervical cancer, and their underlying molecular mechanisms. Methods: Tissues were obtained from cervical cancer patients and their miR-875-5p expression was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Caski or HeLa cells were transfected with miR-875-5p mimics or miR-875-5p inhibitor to assess the effect of miR-875- 5p expression on cell viability, cell cycle, migration, and invasion using Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and Transwell assays. Potential target genes of miR-875-5p were predicted and verified using a dual luciferase reporter assay. In addition, EGFR expression was evaluated by western blot. Results: MicroRNA-875-5p was expressed at low levels in cervical cancer tissues and was related to FIGO stage, lymph node metastasis, pathological grade, vascular involvement, and deep stromal invasion in patients with cervical cancer. MicroRNA-875-5p overexpression inhibited cell viability, migration, and invasion, and caused G0/G1 phase block of Caski and HeLa cells. Moreover, EGFR was the target gene of miR-875-5p and was negatively regulated by miR-875-5p. Reductions in cell viability, migration, invasion, and the number of G0/G1-phase cells were inhibited by EGFR overexpression. Conclusion: MiR-875-5p suppresses cervical cancer cell growth and metastasis by negatively regulating EGFR. Therefore, miR-875-5p can potentially be exploited for the management of cervical cancer.
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