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CLINICAL TRIAL article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1515387

Distinct mRNA Expression Profiles and miRNA Regulators of the PI3K/AKT/mTOR Pathway in Breast Cancer: Insights into Tumor Progression and Therapeutic Targets

Provisionally accepted
Tomasz Sirek Tomasz Sirek 1,2*Katarzyna Król-Jatręga Katarzyna Król-Jatręga 2Przemysław Borawski Przemysław Borawski 3Nikola Zmarzły Nikola Zmarzły 4Dariusz Boron Dariusz Boron 4Piotr Ossowski Piotr Ossowski 4Olga Nawotny-Czupryna Olga Nawotny-Czupryna 4Kacper Boroń Kacper Boroń 2Dominika Janiszewska-Bil Dominika Janiszewska-Bil 4elzbieta mitka-krysiak elzbieta mitka-krysiak 4Beniamin Oskar Grabarek Beniamin Oskar Grabarek 4
  • 1 Consultant, bielsko-biala, Poland
  • 2 Katowice School of Technology, Katowice, Silesian, Poland
  • 3 Independent Researcher, wloclawek, Poland
  • 4 University of Dąbrowa Górnicza, Dąbrowa Górnicza, Poland

The final, formatted version of the article will be published soon.

    Background: Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity of its various subtypes. This study aimed to investigate the differential expression of genes and miRNAs involved in the PI3K/AKT/mTOR signaling pathway, a critical regulator of cancer progression.We analyzed tumor tissues from five breast cancer subtypes-luminal A, luminal B HER2negative, luminal B HER2-positive, HER2-positive, and triple-negative breast cancer (TNBC)-and compared them with non-cancerous tissues. Microarray and qRT-PCR techniques were employed to profile mRNAs and miRNAs, while bioinformatic tools predicted miRNA-mRNA interactions. Statistical analysis was performed with a statistical significance threshold (p) < 0.05. Results: We identified several upregulated genes across all subtypes, with TNBC and HER2-positive cancers showing the most significant changes. Key genes such as COL1A1, COL4A1, PIK3CA, PIK3R1, and mTOR were found to be overexpressed, correlating with increased cancer aggressiveness. miRNA analysis revealed that miR-190a-3p, miR-4729, and miR-19a-3p potentially regulate these genes, influencing the PI3K/AKT/mTOR pathway. For instance, reduced expression of miR-190a-3p may contribute to the overexpression of PIK3CA and other pathway components, enhancing metastatic potential.Our findings suggest that the PI3K/AKT/mTOR pathway and its miRNA regulators play crucial roles in breast cancer progression, particularly in aggressive subtypes like TNBC. The identified miRNAs and mRNAs hold potential as biomarkers for diagnosis and treatment, but further validation in functional studies is required. This study provides a foundation for targeted therapies aimed at modulating this critical pathway to improve breast cancer outcomes.

    Keywords: breast cancer, miRNA, PI3K/Akt/mTOR pathway, molecular marker, mRNA

    Received: 22 Oct 2024; Accepted: 17 Dec 2024.

    Copyright: © 2024 Sirek, Król-Jatręga, Borawski, Zmarzły, Boron, Ossowski, Nawotny-Czupryna, Boroń, Janiszewska-Bil, mitka-krysiak and Grabarek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tomasz Sirek, Consultant, bielsko-biala, Poland

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