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Published on: September 11, 2020
Dysregulated MicroRNAs as Biomarkers or Therapeutic Targets in Cisplatin-Induced Nephrotoxicity: A Systematic Review
Nadine de Godoy Torso1, João Kleber Novais Pereira1, Marília Berlofa Visacri1
1School of Medical Sciences, University of Campinas, Campinas 13083894, Brazil.
Abstract:
The purpose of this systematic review was to map out and summarize scientific evidence on dysregulated microRNAs (miRNAs) that can be possible biomarkers or therapeutic targets for cisplatin nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis of the two miRNAs found to be dysregulated in the majority of studies was performed. A literature search was performed using eight databases for studies published up to 4 July 2021. Two independent reviewers selected the studies and extracted the data; disagreements were resolved by a third and fourth reviewers. A total of 1002 records were identified, of which 30 met the eligibility criteria. All studies were published in English and reported between 2010 and 2021. The main findings were as follows: (a) miR-34a and miR-21 were the main miRNAs identified by the studies as possible biomarkers and therapeutic targets of cisplatin nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a and miR-21, respectively; and (c) studies in humans remain scarce.
Insights
This review identifies microRNAs (miRNAs) like miR-34a and miR-21 as potential biomarkers and therapeutic targets for cisplatin nephrotoxicity. Human studies are limited, highlighting a need for further clinical research.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- Cisplatin is a widely used chemotherapy agent.
- Cisplatin administration can lead to severe kidney damage (nephrotoxicity).
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various diseases, including kidney injury.
Purpose of the Study:
- To systematically review and summarize scientific evidence on microRNAs (miRNAs) as potential biomarkers or therapeutic targets for cisplatin nephrotoxicity.
- To identify miRNAs dysregulated in cisplatin nephrotoxicity across human, animal, and cellular studies.
- To perform an in silico analysis of key dysregulated miRNAs.
Main Methods:
- A systematic literature search was conducted across eight databases up to July 4, 2021.
- Two independent reviewers selected and extracted data from eligible studies, with disagreements resolved by two additional reviewers.
- An in silico analysis was performed on miRNAs identified as dysregulated in the majority of studies.
Main Results:
- 30 studies published between 2010 and 2021 met the eligibility criteria.
- miR-34a and miR-21 were consistently identified as key miRNAs associated with cisplatin nephrotoxicity.
- In silico analysis predicted 124 and 131 validated targets for miR-34a and miR-21, respectively.
- The majority of included studies were preclinical (animal or cell-based), with limited human studies.
Conclusions:
- miR-34a and miR-21 show significant promise as biomarkers and therapeutic targets for mitigating cisplatin nephrotoxicity.
- Further clinical investigations are crucial to validate these findings in human patients.
- The identified targets provide a basis for understanding the molecular mechanisms underlying cisplatin-induced kidney damage.
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