Dual Suppressive Effect of miR-34a on the FOXM1/eEF2-Kinase Axis Regulates Triple-Negative Breast Cancer Growth and Invasion

Bayraktar, Recep; Ivan, Cristina; Bayraktar, Emine; Kanlikilicer, Pınar; Kabil, Nashwa; Kahraman, Nermin; Mokhlis, Hamada A.; Karakaş, Didem; Rodríguez-Aguayo, Cristian; Arslan, Ahmet; Sheng, Jianting; Wong, Stephen T.C.; López-Berestein, Gabriel; Calin, George A.; Özpolat, Bülent

doi:10.1158/1078-0432.ccr-17-1959

Cited by 71 publications

(68 citation statements)

References 52 publications

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“…FOXM1 is overexpressed in breast cancer, including TNBC ( 47 , 48 ). Although multiple molecular characteristics of TNBC have been previously identified, the molecular mechanisms of FOXM1 in TNBC have not been fully elucidated ( 49 ). Breast cancer is a heterogeneous disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of FOXM1 as a specific marker for triple‑negative breast cancer

Tan

Wang²,

Xie

et al. 2018

Int J Oncol

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The present study aimed to identify the therapeutic role of the forkhead box M1 (FOXM1)-associated pathway in triple-negative breast cancer (TNBC). Using a Cancer Landscapes-based analysis, a gene regulatory network model was constructed. The present results demonstrated that FOXM1 occupies a key position in gene networks and is a critical regulatory gene in breast cancer. Using breast carcinoma gene expression data from The Cancer Genome Atlas, it was identified that FOXM1 expression was increased in the basal-like breast cancer subtype compared with other breast cancer subtypes. RNA-sequencing analysis of MDA-MB-231 cells treated with 4 and 10 µl/ml Thiostrepton identified 662 and 5,888 significantly differentially expressed genes, respectively. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses demonstrated that FOXM1 was highly associated with multiple biological processes and was markedly associated with metabolic pathways in TNBC. The use of Search Tool for the Retrieval of Interacting Genes/Proteins provided a critical assessment and integration of protein-protein interactions, and demonstrated the multiple important functions of FOXM1 in TNBC. Real-time cell analysis, reverse transcription-quantitative polymerase chain reaction and immunofluorescence staining were used to assess the anti-tumor activity of Thiostrepton in TNBC cells in vitro. The present results identified that suppression of FOXM1 using Thiostrepton inhibited MDA-MB-231 cell proliferation and the expression of cell cycle-associated genes, including cyclin A2, cyclin B2, checkpoint kinase 1, centrosomal protein 55 and polo like kinase 1. Immunofluorescence staining analysis demonstrated that vimentin, filamentous actin and zinc finger E-box-binding homeobox 1 were all decreased following treatment with Thiostrepton. Furthermore, a BALB/C nude mouse subcutaneous xenograft model was used to verify the function of FOXM1 in vivo. The present results demonstrated that FOXM1 inhibition significantly suppressed MDA-MB-231 cell tumorigenesis in vivo. Overall, the present results suggested that FOXM1 is a key gene that serves important roles in multiple biological processes in TNBC and that it may serve as a novel therapeutic target in TNBC.

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Section: Discussionmentioning

confidence: 99%

Identification of FOXM1 as a specific marker for triple‑negative breast cancer

Tan

Wang²,

Xie

et al. 2018

Int J Oncol

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“…Other effects promoted by miR-34a are the cell-cycle arrest and the apoptosis of TNBC by targeting tRNA i Met and AGO2 [198]. Furthermore, miR-34a negatively regulates the EEF2K and FOXM1 proto-oncogenes, both associated with short-term patient survival [199].…”

Section: Other Non-coding Rnas Relevant In Breast Cancermentioning

confidence: 99%

The network of non-coding RNAs and their molecular targets in breast cancer

et al. 2020

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Background: Non-coding RNAs are now recognized as fundamental components of the cellular processes. Noncoding RNAs are composed of different classes, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Their detailed roles in breast cancer are still under scrutiny. Main body: We systematically reviewed from recent literature the many functional and physical interactions of noncoding RNAs in breast cancer. We used a data driven approach to establish the network of direct, and indirect, interactions. Human curation was essential to de-convolute and critically assess the experimental approaches in the reviewed articles. To enrol the scientific papers in our article cohort, due to the short time span (shorter than 5 years) we considered the journal impact factor rather than the citation number. The outcome of our work is the formal establishment of different sub-networks composed by non-coding RNAs and coding genes with validated relations in human breast cancer. This review describes in a concise and unbiased fashion the core of our current knowledge on the role of lncRNAs, miRNAs and other non-coding RNAs in breast cancer. Conclusions: A number of coding/non-coding gene interactions have been investigated in breast cancer during recent years and their full extent is still being established. Here, we have unveiled some of the most important networks embracing those interactions, and described their involvement in cancer development and in its malignant progression.

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“…There are few studies about EEF2 function in tumor, but a lot about the effect of the EEF2 phosphorylation kinase, EEF2K. EEF2K can promote the growth and metastasis of triple negative breast cancer, as well as paclitaxel resistance of by regulating autophagy activity [25][26][27]. RPL15 is highly expressed in colorectal cancer tissues, affecting cell proliferation and apoptosis [28].…”

Section: Overall Survival Analysis Of Hub Genementioning

confidence: 99%

Identification of key genes controlling docetaxel resistance in patients with breast cancer

Jiang

Qian

2020

Preprint

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Breast cancer is the most common malignant tumor in women. Chemotherapy is a very important part of its comprehensive treatment. Docetaxel is a commonly used chemotherapy drug in breast cancer treatment. However, some patients will develop drug resistance during use. To further explore this issue, we conducted an in-depth analysis on gene expression data of 24 breast cancer patients from GEO. Key module and hub genes were searched through WGCNA network construction, KEGG and GO function analysis, PPI network construction and other methods. Functional analysis revealed that the key module mainly related to drug transport events such as phagocytosis, cell-cell adhesion, and extracellular exosome. TCGA data were used to further verify these hub genes. Finally, we screened out 4 most important key genes, RPS2, EEF2, RPL15 and RPLP1, from 55 hub genes. These findings may highlight some therapeutic targets for predicting, avoiding or overcoming docetaxel resistance.

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Dual Suppressive Effect of miR-34a on the FOXM1/eEF2-Kinase Axis Regulates Triple-Negative Breast Cancer Growth and Invasion

Cited by 71 publications

References 52 publications

Identification of FOXM1 as a specific marker for triple‑negative breast cancer

Identification of FOXM1 as a specific marker for triple‑negative breast cancer

The network of non-coding RNAs and their molecular targets in breast cancer

Identification of key genes controlling docetaxel resistance in patients with breast cancer

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