Dataset Information

MicroRNA-4500 Inhibits Migration, Invasion, and Angiogenesis of Breast Cancer Cells via RRM2-Dependent MAPK Signaling Pathway.

ABSTRACT: With the consideration of the dynamic role of microRNAs (miRNAs) in breast cancer, miRNAs may serve as therapeutic targets, helping to prevent development of therapy resistance, maintain stable disease, and prohibit metastatic spread. We identified the differentially expressed breast cancer-related gene ribonucleotide reductase subunit M2 (RRM2) as the study focus through microarray expression profiles. Next, the upstream regulatory microRNA (miR)-4500 of RRM2 was predicted using bioinformatics website analysis, and their binding was verified by a dual luciferase reporter gene assay. The regulatory effects of miR-4500 on breast cancer cell proliferation, apoptosis, migration, invasion, and capillary-like tube formation of endothelial cells were assessed by gain- and loss-of-function experiments. The experimental data revealed that miR-4500 was downregulated, whereas RRM2 was upregulated in breast cancer cells. Mechanistic analysis revealed that miR-4500 downregulated the RRM2 expression to inactivate the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, miR-4500 exerted anti-tumor effects by targeting RRM2 through suppression of the MAPK signaling pathway in vitro, evidenced by attenuated cancer cell migration and invasion and capillary-like tube formation of endothelial cells. The in vivo experiments further corroborated in vitro results. Collectively, overexpressed miR-4500 could downregulate RRM2 and inhibit activation of the MAPK signaling pathway, thus attenuating breast cancer cell proliferation, invasion, migration, and angiogenesis and promoting breast cancer cell apoptosis.

SUBMITTER: Li S

PROVIDER: S-EPMC7330432 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-4500 Inhibits Migration, Invasion, and Angiogenesis of Breast Cancer Cells via RRM2-Dependent MAPK Signaling Pathway.

Li Shaoying S Mai Huifen H Zhu Yefeng Y Li Guofeng G Sun Jing J Li Guisen G Liang Bichan B Chen Shaojun S

Molecular therapy. Nucleic acids 20200504

With the consideration of the dynamic role of microRNAs (miRNAs) in breast cancer, miRNAs may serve as therapeutic targets, helping to prevent development of therapy resistance, maintain stable disease, and prohibit metastatic spread. We identified the differentially expressed breast cancer-related gene ribonucleotide reductase subunit M2 (RRM2) as the study focus through microarray expression profiles. Next, the upstream regulatory microRNA (miR)-4500 of RRM2 was predicted using bioinformatics ...[more]

PMID: 32615527

Similar Datasets

Project description:Prostate cancer (PCa) testing is currently based on measurement of serum prostate?specific antigen levels and digital rectal examination, which are limited by a low predictive value and the adverse effects associated with overdiagnosis and overtreatment. Recent studies have reported that the abnormal expression of microRNAs (miRNAs) is associated with the mechanism underlying the development of PCa. Thus, the aim of the present study was to investigate the effects of miR?30e and its target gene, M3 muscarinic acetylcholine receptor (CHRM3), on the adhesion, migration, invasion and cell cycle distribution of PCa cells via the mitogen?activated protein kinase (MAPK) signaling pathway. The differentially expressed genes were screened in the Gene Expression Omnibus database from a gene expression microarray (GSE55945) of PCa. PCa tissues and adjacent tissues were collected from patients with PCa. The PC?3 and DU145 human PCa cell lines were treated with activator, inhibitor and siRNAs. The effects of miR?30e on cell adhesion, migration, invasion and cell cycle distribution with the involvement of CHRM3 and the MAPK signaling pathway were investigated. The bioinformatics results demonstrated that the CHRM3 gene and the MAKP signaling pathway were involved in the progression of PCa, and has?miR?30e was selected for further study. The levels of miR?30e were significantly downregulated, while the levels of CHRM3 were obviously upregulated in PCa. CHRM3 was verified as a target gene of miR?30e. Upregulation of miR?30e and downregulation of CHRM3 decreased the levels of p?P38, p?extracellular signal?regulated kinase, p?c?Jun N?terminal kinase, p?c?fos and p?c?JUN, cell adhesion, migration and invasion ability, and the number of cells in the S phase, while they increased the number of cells in the G0 and G1 phases. The findings of the present study suggest that miR?30e inhibited the adhesion, migration, invasion and cell cycle entry of PCa cells by suppressing the activation of the MAPK signaling pathway and inhibiting CHRM3 expression. Thus, miR?30e may serve as a candidate target for the treatment of PCa.

Project description:The enhanced migratory ability of endometrial stromal cells (ESCs) is a key factor in the formation of functional endometrium?like tissues outside the uterine cavity during endometriosis (EMS). Although accumulating evidence has suggested the importance of microRNAs (miRNAs) in the pathogenesis of EMS, the role of particular miRNAs in the invasiveness of ESCs remain poorly understood. In the present study, the function of miRNAs in the invasiveness of ESCs, along with the associated underlying mechanism involved, were investigated. Initially, the expression patterns of miRNAs in the ectopic and eutopic endometrium isolated from patients with EMS were analyzed using microarray. MicroRNA?202?5p (miR?202) was selected for further study due to its previously reported suppressive effects on the invasion in various types of cancers. The expression of miR?202 and K?Ras in eutopic and ectopic endometrioma tissues were detected using reverse transcription?quantitative PCR, immunohistochemistry and western blotting. The migration and invasion ability of ESCs was determined using wound healing and Transwell invasion assays, respectively. Compared with that from healthy individuals, miR?202 expression was demonstrated to be lower in the eutopic endometrium from patients with EMS, which was even lower in ectopic endometrium. Functional experiments in primary ESCs revealed that enhanced miR?202 expression suppressed the cell invasion and migration abilities, which was also accompanied with increased E?cadherin and reduced N?cadherin expression in ESCs, suggesting its potentially suppressive role in epithelial?mesenchymal transition. K?Ras is a well?known regulator of the ERK signaling pathway that was shown to be directly targeted and negatively regulated by miR?202. In addition, K?Ras expression was found to be upregulated in the ectopic endometrium, where it correlated negatively with that of miR?202. Knocking down K?Ras expression mimicked the anti?invasive effects of miR?202 overexpression on ESCs, whilst K?Ras overexpression attenuated the inhibitory role of miR?202 overexpression in ESC invasion. The K?Ras/Raf1/MEK/ERK signaling pathway was also blocked by miR?202 overexpression. These findings suggested that miR?202 inhibited ESC migration and invasion by inhibiting the K?Ras/Raf1/MEK/ERK signaling pathway, rendering miR?202 a candidate for being a therapeutic target for EMS.

Dataset Information

MicroRNA-4500 Inhibits Migration, Invasion, and Angiogenesis of Breast Cancer Cells via RRM2-Dependent MAPK Signaling Pathway.

Publications

MicroRNA-4500 Inhibits Migration, Invasion, and Angiogenesis of Breast Cancer Cells via RRM2-Dependent MAPK Signaling Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure