X-Meeting presentations

MAJOR REGULATORS OF THE MULTI-STEP METASTATIC PROCESS ARE POTENTIAL THERAPEUTIC TARGETS FOR BREAST CANCER MANAGEMENT

Published in 08/11/2023 - ISBN: 978-65-272-0061-1

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Paper Title
MAJOR REGULATORS OF THE MULTI-STEP METASTATIC PROCESS ARE POTENTIAL THERAPEUTIC TARGETS FOR BREAST CANCER MANAGEMENT
Authors
  • Alexandre Luiz korte de Azevedo
  • Tamyres Mingorance Carvalho
  • Cristiane Sato Mara Muller
  • Igor Samesima Giner
  • Jaqueline Carvalho de Oliveira
  • Daniela Fiori Gradia
  • Iglenir João Cavalli
  • Enilze Maria de Souza Fonseca Ribeiro
Modality
Poster
Subject area
Systems Biology and Modeling
Publishing Date
08/11/2023
Country of Publishing
Brazil | Brasil
Language of Publishing
Inglês
Paper Page
https://www.even3.com.br/anais/xmeeting2023/643027-major-regulators-of-the-multi-step-metastatic-process-are-potential-therapeutic-targets-for-breast-cancer-managem
ISBN
978-65-272-0061-1
Keywords
Breast cancer metastasis; Feed-forward loops; microRNAs; Network analysis.
Summary
Metastasis is a multi-step process that leads to the dissemination of tumor cells to new sites and, consequently, to multi-organ neoplasia. Although most lethal breast cancer cases are related to metastasis occurrence, little is known about the dysregulation of each step, and clinicians still lack reliable therapeutic targets for metastasis impairment. To fill these gaps, we constructed and analyzed gene regulatory networks of each metastasis step (cell adhesion loss, epithelial-to-mesenchymal transition, and angiogenesis). Initially, we obtained a list of differentially expressed genes (including transcription factors) and miRNAs in the comparison of breast cancer samples regarding non-tumor breast samples (TCGA dataset; P-value < 0.001). Next, we filtered our differentially expressed genes according to the hallmark collection of the MSigDB (v. 7.5.1) database; Only those genes related to cell adhesion (apical junction and apical surface hallmarks), epithelial-to-mesenchymal transition, and angiogenesis (homonym hallmark) were maintained, generating three different gene sets, which were used to form three separated networks. Through topological analysis, we identified E2F1, EGR1, EZH2, JUN, TP63, and miR-200c-3p as general hub-regulators; FLI1 for cell-adhesion loss specifically, and TRIM28, TCF3, and miR-429 for angiogenesis. Applying the FANMOD algorithm, we identified 60 coherent feed-forward loops regulating metastasis-related genes associated with distant metastasis-free survival prediction. The miR-139-5p, miR-200c-3p, miR-454-3p, and miR-1301-3p, among others, were the FFL’s mediators. The expression of the hub-regulators and mediators was observed to impact overall survival and to go along with metastasis occurrence. Lastly, we selected 12 key regulators and observed that they are potential therapeutic targets for canonical and candidate antineoplastics and immunomodulatory drugs, like trastuzumab, goserelin, and calcitriol. Our results highlight the relevance of miRNAs in mediating feed-forward loops and regulating the expression of metastasis-related genes. Altogether, our results contribute to understanding the multi-step metastasis complexity and identifying novel therapeutic targets and drugs for breast cancer management.
Title of the Event
X-Meeting / BSB 2023
City of the Event
Curitiba
Title of the Proceedings of the event
X-Meeting presentations
Name of the Publisher
Even3
Means of Dissemination
Meio Digital

How to cite

AZEVEDO, Alexandre Luiz korte de et al.. MAJOR REGULATORS OF THE MULTI-STEP METASTATIC PROCESS ARE POTENTIAL THERAPEUTIC TARGETS FOR BREAST CANCER MANAGEMENT.. In: X-Meeting presentations. Anais...Curitiba(PR) Campus da indústria, 2023. Available in: https//www.even3.com.br/anais/xmeeting2023/643027-MAJOR-REGULATORS-OF-THE-MULTI-STEP-METASTATIC-PROCESS-ARE-POTENTIAL-THERAPEUTIC-TARGETS-FOR-BREAST-CANCER-MANAGEM. Access in: 31/08/2025

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