Introduction Cervical cancer is the second most common type of cancer and the third leading cause of cancer deaths in females in developing countries. Recent studies showed that long non-coding RNAs play a key role in human cancers. However, the molecular mechanisms underlying the initiation and progression of cervical cancer remained to be further explored. Material and methods In this study, we explored the differential expression of lncRNAs and mRNAs in cervical cancer progression by analyzing the public dataset GSE63514. Next, PPI and co-expression networks were constructed to reveal the potential roles of cervical cancer related mRNAs and lncRNAs. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to explore functions of differentially expressed genes (DEGs) in cervical cancer. Results In the present study, we observed that 3021 mRNAs were up-regulated and 1605 mRNAs were down-regulated in cervical cancer progression. Meanwhile, we for the first time found that 172 lncRNAs were up-regulated and 106 lncRNAs were down-regulated in cervical cancer progression. Co-expression network analysis showed that lncRNAs were widely co-expressed with cell cycle related genes in cervical cancer, implicating the important roles of these lncRNAs in cell proliferation regulation. Of note, we identified two hub lncRNA-mRNA networks involved in regulating various biological processes in cervical cancer progression. Conclusions Our results identified key mRNAs and lncRNAs in cervical cancer progression. This study will provide novel insights to explore the potential mechanisms underlying cervical cancer progression.
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.
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.
Background: Cervical cancer remains a serious threat to women worldwide. Thus, effective strategies to treat cervical cancer are urgently needed. Bcl-2-associated athanogene 3 (Bag3) has been shown to be increased in several malignant neoplasms. However, little is known about the function of Bag3 in cervical cancer. We aimed to evaluate the function of Bag3 in cervical cancer progression.Method: qRT-PCR was carried out to test mRNA expression of Bag3, SLC7A11 and SLC3A2. Western blot analysis was conducted to detect protein expression of Bag3, SLC7A11 and SLC3A2. Cell proliferation was assessed using CCK-8, EdU and Colony formation assay. Flow cytometry assay was used to determine the frequency of IFN-γ- or TNF-α-producing CD8+ T cells. Transwell migration and invasion assay were carried out to detect cell migration and invasion capacity. Immunohistochemical staining was carried out to assess Bag3 and CD3 expressionResults: Bag3 was obviously elevated in cervical cancer tissues than in the adjacent normal tissues. Bag3 mRNA was upregulated in different cervical cancer cells (SiHa, C-33A, HT-3, and HeLa cells). SiHa cell proliferation, colony formation, and migration/invasion capacity were enhanced by Bag3 overexpression. Bag3 inhibited the immune response in cervical cancer. After C57BL6 mice were injected with Bag3-overexpressing SiHa cells, infiltrating CD3+ T cells around tumors were reduced. IFN-γ- and TNF-α-producing CD8+ T cells in tumor sections were remarkably inhibited by Bag3. Moreover, Ki-67+‑ and CD107a-producing CD8+ T cells were also suppressed. Bag3 repressed SiHa cell ferroptosis. Bag3 deletion inhibited cervical cancer development by improving the immune response and inducing ferroptosis. Conclusions: Taken together, these results indicated that Bag3 contributes to cervical cancer progression by impairing immune response and repressing cell ferroptosis.
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