Tumor Biology

, Volume 36, Issue 6, pp 4203–4212 | Cite as

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

  • Seyed Hamid Aghaee-Bakhtiari
  • Ehsan Arefian
  • Mahmood Naderi
  • Farshid Noorbakhsh
  • Vahideh Nodouzi
  • Mojgan Asgari
  • Pezhman Fard-Esfahani
  • Reza Mahdian
  • Masoud Soleimani
Research Article

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.

Keywords

miR-23a miR-23b Prostate cancer MAPK pathway JAK/STAT pathway 

Notes

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.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Seyed Hamid Aghaee-Bakhtiari
    • 1
    • 4
    • 10
  • Ehsan Arefian
    • 2
    • 4
  • Mahmood Naderi
    • 3
    • 4
  • Farshid Noorbakhsh
    • 5
  • Vahideh Nodouzi
    • 1
  • Mojgan Asgari
    • 6
    • 7
  • Pezhman Fard-Esfahani
    • 8
  • Reza Mahdian
    • 1
  • Masoud Soleimani
    • 9
  1. 1.Molecular Medicine Department, Biotechnology Research CenterPasteur Institute of IranTehranIran
  2. 2.Department of Microbiology, School of Biology, College of ScienceUniversity of TehranTehranIran
  3. 3.Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research InstituteTehran University of Medical SciencesTehranIran
  4. 4.Department of Molecular Biology and Genetic EngineeringStem Cell Technology Research CenterTehranIran
  5. 5.Department of Immunology, Faculty of MedicineTehran University of Medical SciencesTehranIran
  6. 6.Oncopathology Research CenterIran University of Medical Science (IUMS)TehranIran
  7. 7.Pathology Department of Hasheminejad Kidney CenterIran University of Medical SciencesTehranIran
  8. 8.Department of BiochemistryPasteur Institute of IranTehranIran
  9. 9.Department of HematologyTarbiat Modares UniversityTehranIran
  10. 10.Department of Modern Sciences and TechnologiesSchool of Medicine, Mashhad University of Medical SciencesMashhadIran

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