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MAPK and JAK/STAT pathways targeted by miR-23a and miR-23b in prostate cancer: computational and in vitro approaches

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Tumor Biology

Abstract

The long-lasting inadequacy of existing treatments for prostate cancer has led to increasing efforts for developing novel therapies for this disease. MicroRNAs (miRNAs) are believed to have considerable therapeutic potential due to their role in regulating gene expression and cellular pathways. Identifying miRNAs that efficiently target genes and pathways is a key step in using these molecules for therapeutic purposes. Moreover, computational methods have been devised to help identify candidate miRNAs for each gene/pathway. MAPK and JAK/STAT pathways are known to have essential roles in cell proliferation and neoplastic transformation in different cancers including prostate cancer. Herein, we tried to identify miRNAs that target these pathways in the context of prostate cancer as therapeutic molecules. Genes involved in these pathways were analyzed with various algorithms to identify potentially targeting miRNAs. miR-23a and miR-23b were then selected as the best potential candidates that target a higher number of genes in these pathways with greater predictive scores. We then analyzed the expression of candidate miRNAs in LNCAP and PC3 cell lines as well as prostate cancer clinical samples. miR-23a and miR-23b showed a significant downregulation in cell line and tissue samples, a finding which is consistent with overactivation of these pathways in prostate cancer. In addition, we overexpressed miR-23a and miR-23b in LNCAP and PC3 cell lines, and these two miRNAs decreased IL-6R expression which has a critical role in these pathways. These results suggest the probability of utilizing miR-23a and miR-23b as therapeutic targets for the treatment of prostate cancer.

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Acknowledgments

The authors appreciate the Pasteur Institute of Iran, Tehran, Iran for providing technical support. The authors are thankful to Vahid Haghpanah and Mohsen Khorashadizadeh for reading the manuscript and critical discussions. The authors are grateful to Zahra Masoumi and Fatemeh Kohram for editing the manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Funding

This study was funded by the Stem Cell Technology Research Center, Tehran, Iran.

Authors’ contributions

Seyed Hamid Aghaee-Bakhtiari carried out the practical tests and drafted the manuscript. Ehsan Arefian carried out the study design and drafting. Mahmood Naderi participated in the design of the study and drafting. Farshid Noorbakhsh participated in study design, data analysis, and draft preparation. Vahideh Nodouzi helped in clinical sample gathering and assisted in data analysis. Mojgan Asgari aided sample gathering and analyzed the stage of tumor samples. Pezhman Fard-Esfahani participated in data analysis and assisted in drafting the manuscript. Reza Mahdian helped in study design and aided in manuscript editing. Masoud Soleimani assisted in study design, data analysis, and draft preparation. All authors read and approved the final manuscript.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, No. 358, 12th Farwardin Ave, St, Tehran, Iran

    Seyed Hamid Aghaee-Bakhtiari, Vahideh Nodouzi & Reza Mahdian

  2. Department of Microbiology, School of Biology, College of Science, University of Tehran, Enqelab St, Tehran, Iran

    Ehsan Arefian

  3. Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Jalal Ale Ahmad Highway, Tehran, Iran

    Mahmood Naderi

  4. Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, No. 9 East 2nd St, Saadat Abad St, Tehran, Iran

    Seyed Hamid Aghaee-Bakhtiari, Ehsan Arefian & Mahmood Naderi

  5. Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Enqelab St, Tehran, Iran

    Farshid Noorbakhsh

  6. Oncopathology Research Center, Iran University of Medical Science (IUMS), Hemmat Highway, Tehran, Iran

    Mojgan Asgari

  7. Pathology Department of Hasheminejad Kidney Center, Iran University of Medical Sciences, Valiasr St, Tehran, Iran

    Mojgan Asgari

  8. Department of Biochemistry, Pasteur Institute of Iran, No. 358, 12th Farwardin Ave, Jomhhoori St, Tehran, Iran

    Pezhman Fard-Esfahani

  9. Department of Hematology, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran, Iran

    Masoud Soleimani

  10. Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Vakilabad Highway, Mashhad, Iran

    Seyed Hamid Aghaee-Bakhtiari

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  1. Seyed Hamid Aghaee-Bakhtiari
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  2. Ehsan Arefian
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Correspondence to Masoud Soleimani.

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Aghaee-Bakhtiari, S.H., Arefian, E., Naderi, M. et al. MAPK and JAK/STAT pathways targeted by miR-23a and miR-23b in prostate cancer: computational and in vitro approaches. Tumor Biol. 36, 4203–4212 (2015). https://doi.org/10.1007/s13277-015-3057-3

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  • DOI: https://doi.org/10.1007/s13277-015-3057-3

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