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Crosstalk Between m6A RNA Methylation and miRNA Biogenesis in Cancer: An Unholy Nexus
P J Jayasree1, Shalmoli Dutta1, Pragati Karemore1
1Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal-Malkajgiri District, Hyderabad, Telangana, 500078, India.
Abstract:
N6-methyladenosine (m6A) is one of the most prevalent internal reversible chemical modification of RNAs in eukaryotes, which has attracted widespread attention recently owing to its regulatory roles in a plethora of normal developmental processes and human diseases like cancer. Deposition of the m6A mark on RNAs is mediated by the dynamic interplay between m6A regulatory proteins such as m6A RNA methyltransferases (m6A writers), m6A RNA demethylases (m6A erasers) and m6A RNA binding proteins (m6A readers). m6A regulators are ectopically expressed in various cancer types, often leading to aberrant expression of tumor-suppressor and oncogenic mRNAs either directly or indirectly via regulating the biogenesis of non-coding RNAs like miRNAs. miRNAs are tiny regulators of gene expression, which often impact various hallmarks of cancer and thus influence tumorigenesis. It is becoming increasingly clear that m6A RNA modification impacts biogenesis and function of miRNAs, and recent studies have interestingly, uncovered many miRNAs whose biogenesis and function are regulated by m6A writers, erasers and readers. In this review, we discuss various mechanisms by which m6A RNA methylation regulates miRNA biogenesis, the functional crosstalk between m6A RNA methylation and miRNAs and how it modulates various aspects of tumorigenesis. The potential of m6A RNA methylation regulated miRNAs as biomarkers and novel therapeutic targets to treat various cancers is also addressed.
Insights
N6-methyladenosine (m6A) RNA modification regulates microRNA (miRNA) biogenesis and function, impacting cancer development. This interplay offers potential for novel cancer biomarkers and therapies.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- N6-methyladenosine (m6A) is a prevalent RNA modification involved in gene regulation.
- m6A regulators (writers, erasers, readers) influence mRNA and non-coding RNA expression.
- Aberrant m6A regulation is linked to various human cancers.
Purpose of the Study:
- To review mechanisms of m6A-mediated regulation of miRNA biogenesis.
- To explore the functional crosstalk between m6A and miRNAs in tumorigenesis.
- To discuss the potential of m6A-regulated miRNAs as cancer biomarkers and therapeutic targets.
Main Methods:
- Literature review of studies on m6A RNA methylation and miRNAs.
- Analysis of regulatory mechanisms involving m6A writers, erasers, and readers.
- Synthesis of findings on m6A-miRNA interactions in cancer.
Main Results:
- m6A modification impacts miRNA biogenesis and function.
- m6A regulators modulate tumor-suppressor and oncogenic miRNA expression.
- Functional crosstalk between m6A and miRNAs influences cancer hallmarks.
Conclusions:
- m6A RNA methylation plays a significant role in cancer development via miRNA regulation.
- m6A-regulated miRNAs represent promising biomarkers for cancer diagnosis.
- Targeting m6A-miRNA pathways offers novel therapeutic strategies for cancer treatment.
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