Background: Cervical carcinoma is one of the most common malignant gynecological tumors and is associated with high rates of morbidity and mortality. Early diagnosis and early treatment can reduce the mortality rate of cervical cancer. However, there is still no specific biomarkers for the diagnosis and detection of cervical cancer prognosis. Therefore, it is greatly urgent in searching biomarkers correlated with the diagnosis and prognosis of cervical cancer. Results: The mRNA and microRNA expression profile datasets (GSE7803, GSE9750, GSE63514, and GSE30656) were downloaded from the Gene Expression Omnibus database (GEO). The three microarray datasets were integrated to one via integrated bioinformatics. Differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained by R software. The protein–protein interaction (PPI) networks of the DEGs were performed from the STRING database and further visualized by Cytoscape software. A total of 83 DEGs and 14 DEMs were screened from the microarray expression profile datasets. The miRNAs validated to be associated with cervical cancer were obtained using HMDD online website and the target genes of DEMs were identified using the miRWalk2.0 online database. ESR1, PPP1R3C, NSG1 , and TMPRSS11D were the gene targets of hsa-miR-21; the targets of hsa-miR-16 were GYS2, ENDOU , and KLF4 . These targets were all downregulated in cervical cancer. Finally, we verified the expression of those targets in cervical tissues from TCGA and GTEx databases and analyzed their relationship with survival of cervical cancer patients. In the end, the expression of key genes in cervical cancer tissues was verified via experiment method, we found KLF4 and ESR1 were downregulated in tumor tissues. Conclusion: This study indicates that KLF4 and ESR1 are downregulated by the upregulated miR21 and miRNA16 in cervical cancer, respectively, using bioinformatics analysis, and the lower expression of KLF4 and ESR1 is closely related to the poor prognosis. They might be of clinical significance for the diagnosis and prognosis of cervical cancer, and provide effective targets for the treatment of cervical cancer.
Background: Ovarian cancer (OC), a representative female reproductive system tumor, is one of the most malignant tumors in female. The most important reason for its poor prognosis is because of its high rate of chemotherapy resistance. Results: This study aims to explore the effects of miR-21 on the chemotherapy resistance of OC cells. The functions of miR-21 on proliferation, migration and invasion of OC cells were assessed by transwell, clonal formation and CCK8 assay. Expression levels of miR-21, P-gp and CD44v6 in SKOV3 (cisplatin sensitive) cells and SKOV3/DDP (cisplatin resistant) cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Si-CD44v6 was transfected into OC cells to detect the influence on P-glycoprotein (P-gp) expression. Immunofluorescence was used to detect the localization of CD44v6 and P-gp in cell. Co-immunoprecipitation was used to detect the relationship between CD44v6 and P-gp. Results showed that miR-21 expression in cisplatin-resistant SKOV3/DDP cells was significantly higher than that in SKOV3 cells, at the same time, cells proliferation, as well as invasion and migration ability were enhanced after the miR-21 mimics transfected into SKOV3 cisplatin-sensitive cells. Furthermore, miR-21 expression level affected the CD44v6 and P-gp expression. Immunofluorescence and co-immunoprecipitation showed that CD44v6 and P-gp protein could interact. Conclusion: In conclusion, the high miR-21 expression level could increase the proliferation, invasion, and migration ability of OC cells. And the interaction of CD44v6 and P-gp may mediate miR-21 involvement in chemotherapy resistance of OC cells.
Pelvic organ prolapses (PoP) notably reduces the quality of life in elderly populations due to bladder and bowel dysfunction, incontinence, and coital problems. extracellular matrix (ecM) disorder is a pivotal event in the progression of PoP, but to date, its specific underlying mechanism remains unclear. The ligaments of patients with PoP and healthy controls were collected to compare the expression of Homeobox11 (HoXa11) and transforming growth factor β (TGF-β1) via immunohistochemical analysis. HoXa11 and TGF-β1 were overexpressed or knocked down in fibroblast cells to explore their effects on the expression of collagen and matrix metalloproteinases (MMPs). HoXa11 and TGF-β1 were greatly reduced in the ligaments of patients with PoP. The overexpression and downregulation of HoXa11 and TGF-β1 can mediate ecM disorder via regulating expression of collagen (col) and MMPs. in addition, HoXa11 and TGF-β1 exerted synergistic effect on the expression of col and MMPs. The present study identified that HOXA11 and TGF-β1 serve critical roles in mediating ecM disorders, which may be of clinical significance for the diagnosis and treatment of patients with PoP.
Previous studies have identified microRNA-200b (miR-200b) as a powerful regulator of epithelial-mesenchymal transition (EMT) via the control of gene expression. EMT is a critical event that is associated with the initiation of malignant tumor metastasis. A lack of E-cadherin expression and overexpression of vimentin are hallmarks of EMT. It is well‑known that RhoE, which is associated with regulation of the actin cytoskeleton and migration via alterations in cell motility, regulates the expression of E-cadherin, matrix metalloproteinase-9 (MMP-9) and vimentin. However, it remains to be elucidated whether miR‑200b may alter the molecular behavior of RhoE. The present study aimed to determine whether miR‑200b was able to regulate the EMT of cervical cancer, in order to control metastasis. In addition, the correlation between miR‑200b and RhoE, E‑cadherin and vimentin expression was investigated. Notably, miR‑200b was shown to inhibit the function of RhoE and suppress the EMT of cervical cancer. Furthermore, HeLa cells were transfected with miR‑200b mimics or inhibitors, and the protein expression levels of E‑cadherin, MMP‑9, vimentin and RhoE were subsequently detected. A Transwell assay was also conducted, in order to observe the metastatic ability of the HeLa cells. In addition, a luciferase reporter assay was performed using luciferase reporter vectors containing the full length 3'‑untranslated region (UTR) of RhoE; miR‑200b was able to significantly suppress relative luciferase activity by targeting the 3'‑UTR of RhoE. These results suggested that miR‑200b may markedly inhibit metastatic potential by regulating cell EMT and inhibiting RhoE; therefore, miR-200b may be considered an effective target for the treatment of patients with highly metastatic cervical cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.