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Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance
Ligia I Torsin1, George E D Petrescu2,3, Alexandru A Sabo4
1Department of Anesthesiology and Critical Care, Elias Clinical Emergency Hospital, 011461 Bucharest, Romania.
Abstract:
Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered "non-functional" ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer is it possible to translate the knowledge about ncRNAs and their modifications into clinical practice.
Insights
Dysregulated non-coding RNAs (ncRNAs) and their modifications are hallmarks of cancer. Understanding these ncRNA modifications is crucial for developing new diagnostic and therapeutic strategies in oncology.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Non-coding RNAs (ncRNAs) are increasingly recognized for their roles in cancer.
- Alterations in the ncRNA transcriptome are a novel hallmark of cancer.
- Mechanisms regulating ncRNAs, particularly post-transcriptional modifications, are emerging areas of research.
Purpose of the Study:
- To review common regulatory modifications of ncRNAs in cancer.
- To discuss chemical modifications (e.g., m5C, m6A) and editing (e.g., ADAR, APOBEC) of microRNAs, long non-coding RNAs, and circular RNAs.
- To highlight the clinical relevance of understanding ncRNA modifications for cancer diagnostics and therapeutics.
Main Methods:
- Literature review of recent research on ncRNA modifications in cancer.
- Synthesis of information on reversible (chemical) and non-reversible (editing) modifications.
- Focus on microRNAs, long non-coding RNAs, and circular RNAs.
Main Results:
- Dysregulated levels of ncRNAs are prevalent across various cancer types.
- Specific chemical modifications and editing events are altered in cancer and contribute to tumorigenesis.
- These modifications impact the function of ncRNAs, influencing cancer development.
Conclusions:
- ncRNA modifications represent a critical regulatory layer in cancer.
- Understanding these modifications is essential for translating ncRNA research into clinical applications.
- Targeting ncRNA modifications holds potential for novel cancer therapies and diagnostics.
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