Kanikah Mehndiratta, MSc, University of Glasgow
A lot of recent approaches to targeting different diseases have been at the transcriptional level where the root cause could be analyzed and/or eliminated. Obesity is one such condition that is being approached through miRNA mimicking as a therapeutic tool in a recent study published in the Molecular Therapy journal. The study predicts mimicking of miRNA to be a guide for the drug development process against obesity.
miRNAs as potential therapeutic targets:
miRNAs are a type of single-stranded, non-coding mRNAs that prove useful in the regulation of gene expression. From primary to precursors, and finally, a mature miRNA mostly interacts with the 3’ UTR of its target mRNA, mainly repressing the transcriptional function of the associated gene. It may interact with the 5’ UTR, the promoter region, or even the coding sequences. It might also be involved in translational activation, where the interaction is believed to be dependent on a lot of different factors such as location, abundancy, affinity, and the target mRNAs. Due to this dynamic regulatory role during transcription, especially in metabolic processes, they are being considered as potential therapeutic targets for various conditions.
Targeting obesity through miRNA mimicking:
The comorbidities associated with obesity such as insulin resistance, high blood pressure, stroke, cardiovascular diseases, sleep apnoea, etc. are reported to be developing due to dysregulation of many different miRNAs in white adipose tissues and liver muscles. The particular miRNA focused on in this Spain study is the miR-21 in the white adipose tissues. The expression level of the normal miRNA in diseased conditions was analyzed to predict the effect of a mimic in the functionality of the tissues and consider its potential application in therapy for obesity. The miR-21 levels were lower in normal-weight mice and humans in comparison to a diabetic obese sample. The mimic used was also shown to affect the functionality of the adipose tissues and was observed to significantly enhance gene expression in thermogenesis and browning by directly interfering with the activity of the RNA-induced silencing complex leading to a gain of function and increasing metabolic rate.
Results:
The artificial mi-RNA mimic in-vivo treatment, also called the miRNA replacement therapy, blocked weight gain by interfering with the p53, TGFβ1 signalling pathways that were causing metabolic activity enhancement. This study thus suggested a therapeutic potential to manage obesity and associated comorbidities.
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References:
1. Lhamyani, S., Gentile, A-M., Giráldez-Pérez, R. M., et al. (2020). miR-21 blocks obesity in mice: a potential therapy for humans. medRxiv. https://doi.org/10.1101/2020.10.27.20219915
2. O’Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018). Overview of microRNA biogenesis, mechanisms of actions, and circulation. Frontiers in endocrinology, 9, 402. https://doi.org/10.3389/fendo.2018.00402
About author:
Kanikah Mehndiratta is an avid researcher in the field of Genetics with a background in Biotechnology. She is a postgraduate from the University of Glasgow in their Medical Genetics and Genomics program. Currently, based in Chandigarh as a Scientific Writer, she involves herself mainly in projects related to neurological disorders. Apart from academics, she likes to read novels, travel and is involved in volunteer work mostly.
LinkedIn profile- https://www.linkedin.com/in/kanikah-mehndiratta-301830171
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