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MicroRNAs Targeting MYC Expression: Trace of Hope for Pancreatic Cancer Therapy. A Systematic Review

Authors Shams R, Asadzadeh Aghdaei H, Behmanesh A, Sadeghi A, Zali M, Salari S, Padrón JM

Received 13 January 2020

Accepted for publication 13 March 2020

Published 1 April 2020 Volume 2020:12 Pages 2393—2404

DOI https://doi.org/10.2147/CMAR.S245872

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Roshanak Shams,1 Hamid Asadzadeh Aghdaei,1 Ali Behmanesh,2 Amir Sadeghi,1 Mohammadareza Zali,1 Sina Salari,3 José M Padrón4

1Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Student Research Committee, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran; 3Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4BioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Universidad de la Laguna, La Laguna, Spain

Correspondence: Roshanak Shams; Ali Behmanesh
Email shams.rosha.86@gmail.com; aa.behmanesh@gmail.com

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and a major health problem worldwide. There were no major advances in conventional treatments in inhibiting tumor progression and increasing patient survival time. In order to suppress mechanisms responsible for tumor cell development such as those with oncogenic roles, more advanced therapeutic strategies should be sought. One of the most important oncogenes of pancreatic cancer is the MYC gene. The overexpression of MYC can activate many tumorigenic processes such as cell proliferation and pancreatic cancer cell invasion. MiRNAs are important molecules that are confirmed by targeting mRNA transcripts to regulate the expression of the MYC gene. Therefore, restoring MYC-repressing miRNAs expression tends to be an effective method of treating MYC-driven cancers.
Objective: The purpose of this study was to identify all validated microRNAs targeting C-MYC expression to inhibit PDAC progression by conducting a systematic review.
Methods: In this systematic review study, the papers published between 2000 and 2020 in major online scientific databases including PubMed, Scopus, and Web of Science were screened, following inclusion and exclusion criteria. We extracted all the experimental studies that showed miRNAs could target the expression of the MYC gene in PDAC.
Results: Eight papers were selected from a total of 89 papers. We found that six miRNAs (Let-7a, miR-145, miR-34a, miR-375, miR-494, and miR-148a) among the selected studies were validated for targeting MYC gene and three of them confirmed Let-7a as a direct MYC expression regulator in PC cells. Finally, we summarized the latest shreds of evidence of experimentally validated miRNAs targeting the MYC gene with respect to PDAC’s therapeutic potential.
Conclusion: Restoring the expression of MYC-repressing miRNAs tends to be an effective way to treat MYC-driven cancers such as PDAC. Several miRNAs have been proposed to target this oncogene via bioinformatics tools, but only a few have been experimentally validated for pancreatic cancer cells and models. Further studies should be conducted to find the interaction network of miRNA-MYC to develop more successful therapeutic strategies for PC, using the synergistic effects of these miRNAs.

Keywords: micro RNA, pancreatic cancer, MYC, cancer therapy

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