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RNA modifications and cancer
Research Guide
What is RNA modifications and cancer?
RNA modifications and cancer refers to the study of chemical alterations to RNA molecules, such as N6-methyladenosine (m6A) and N7-methylguanosine (m7G), that regulate gene expression, RNA stability, translation, and other processes dysregulated in cancer development, progression, therapy response, and drug resistance.
The field encompasses over 112,541 works on RNA modifications in cancer contexts. High-throughput sequencing analysis tools like 'Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2' by Love et al. (2014) with 93,376 citations enable detection of modification-associated expression changes. Recent preprints highlight m6A regulation in oncogenesis and METTL1-mediated m7G in immunotherapy.
Research Sub-Topics
N6-Methyladenosine RNA Methylation
m6A modification dynamics regulated by writers (METTL3/14), erasers (FTO/ALKBH5), and readers (YTHDF1-3) control mRNA stability, translation, and splicing. Cancer studies reveal METTL3 overexpression driving leukemia, glioblastoma, and hepatocellular carcinoma proliferation.
N1-Methyladenosine in tRNA and rRNA
m1A modifications at tRNA wobble positions (DKC1/TRMT61B) and rRNA ensure translation fidelity and ribosome biogenesis. Research links m1A hypomodification to ribosomal frameshifting in cancer and FTO-independent epitranscriptomic regulation.
5-Methylcytosine RNA Modifications
m5C in tRNA, rRNA, and mRNA regulated by NSUN2/NOP2 methyltransferases affects translation efficiency and stress granule formation. Studies demonstrate m5C accumulation in glioblastoma and bladder cancer correlating with poor prognosis.
Pseudouridine Synthases in Cancer
PUS enzymes (DKC1, PUS1/7) catalyze ψ formation stabilizing RNA structure and translation. DKC1 amplification in cancers enhances ribosome biogenesis, while ψ modifications evade immune detection in tumor-derived extracellular vesicles.
Alternative Polyadenylation RNA Regulation
APA shifts 3'UTR length altering miRNA binding, mRNA stability, and protein isoforms, dysregulated by CFIm25 depletion in cancer. Proliferation/survival genes acquire shorter 3'UTRs escaping repression in breast, lung, and prostate tumors.
Why It Matters
RNA modifications influence cancer through control of RNA metabolism, with m6A affecting stability and translation via writer, eraser, and reader proteins, as detailed in 'The epitranscriptome meets non-coding RNA: m6A-mediated regulation in oncogenesis and therapy'. METTL1 catalyzes m7G on tRNA to stabilize structure and enhance translation in cancer, per 'The emerging roles of METTL1-mediated tRNA m 7 G methylation in cancer development and immunotherapy'. The National Cancer Institute's Notice of Special Interest targets mechanistic insights into these modifications for cancer biology. STORM Therapeutics develops small molecule drugs targeting RNA modifying enzymes for cancer treatment, as announced in their strategic partnership with AlidaBio. A new SMART tool profiles RNA modifications to support precise cancer therapies.
Reading Guide
Where to Start
'Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2' by Love et al. (2014), as it provides the foundational statistical method for analyzing RNA-seq data central to studying modification-associated expression in cancer, cited 93,376 times.
Key Papers Explained
'Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2' by Love et al. (2014) enables differential analysis building on alignment from 'STAR: ultrafast universal RNA-seq aligner' by Dobin et al. (2012) and quantification via 'featureCounts' by Liao et al. (2013). 'Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles' by Subramanian et al. (2005) interprets these profiles for modification pathways. HISAT by Kim et al. (2015) and RSEM by Li and Dewey (2011) extend alignment and quantification for complex cancer transcriptomes.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Recent preprints focus on m6A in oncogenesis, METTL1 m7G in immunotherapy, and FTO in resistance. NCI NOSI calls for mechanistic studies. STORM Therapeutics advances RNA enzyme inhibitors clinically. New SMART tool and GitHub resources like RNAmodR, NetRNApan support high-resolution mapping.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Moderated estimation of fold change and dispersion for RNA-seq... | 2014 | Genome biology | 93.4K | ✓ |
| 2 | Gene set enrichment analysis: A knowledge-based approach for i... | 2005 | Proceedings of the Nat... | 54.1K | ✓ |
| 3 | STAR: ultrafast universal RNA-seq aligner | 2012 | Bioinformatics | 52.5K | ✓ |
| 4 | Cutadapt removes adapter sequences from high-throughput sequen... | 2011 | EMBnet journal | 33.6K | ✓ |
| 5 | The SILVA ribosomal RNA gene database project: improved data p... | 2012 | Nucleic Acids Research | 31.8K | ✓ |
| 6 | featureCounts: an efficient general purpose program for assign... | 2013 | Bioinformatics | 27.0K | ✓ |
| 7 | HISAT: a fast spliced aligner with low memory requirements | 2015 | Nature Methods | 24.6K | ✓ |
| 8 | RSEM: accurate transcript quantification from RNA-Seq data wit... | 2011 | BMC Bioinformatics | 22.3K | ✓ |
| 9 | Full-length transcriptome assembly from RNA-Seq data without a... | 2011 | Nature Biotechnology | 21.8K | ✓ |
| 10 | HTSeq—a Python framework to work with high-throughput sequenci... | 2014 | Bioinformatics | 21.7K | ✓ |
In the News
Harnessing the power of RNA epigenetics | Cambridge, UK
breakthrough small molecule drugs that precisely reprogram cells through RNA biology for the treatment of cancer, inflammation, viruses and CNS diseases.
STORM Therapeutics and AlidaBio Announce Strategic ...
**STORM Therapeutics is a clinical-stage biotechnology company pioneering cellular reprogramming through RNA modifications to treat disease. Its world leading understanding of RNA modifying enzymes...
RNA Modifications in Cancer Biology
Through this Notice of Scientific Interest (NOSI), the National Cancer Institute intends to stimulate research on the role of RNA modifications in the area of cancer biology. Despite the recognitio...
Notice of Special Interest (NOSI): RNA Modifications in Cancer Biology
The purpose of this Notice of Special Interest (NOSI) is to stimulate research on the role of RNA modifications in the area of cancer biology. Despite the recognition that RNA modifications and edi...
New SMART tool maps RNA modifications to tackle cancer ...
Researchers have developed the first high-throughput tool to rapidly profile RNA modifications – a breakthrough that could lead to more precise treatments for cancer and antibiotic-resistant infect...
Code & Tools
RNA modification, which is evolutionarily conserved, is crucial for modulating various biological functions and disease pathogenesis. High resoluti...
Scripts used to extract curated lists of RNA modification enzymes and assess their tissue-specificity across multiple species and tissues, as well ...
For further details have a look at the vignette or the additional packages for implementation examples:
**RNA Framework**is a modular toolkit developed to deal with RNA structure probing and post-transcriptional modifications mapping high-throughput d...
CaDRReS-Sc is a framework for analyzing drug response heterogeneity based on single-cell RNA-seq data ### License GPL-3.0 license
Recent Preprints
The epitranscriptome meets non-coding RNA: m6A-mediated regulation in oncogenesis and therapy
The field of epitranscriptomics discovered N6-methyladenosine (m6A) modifications, which function as fundamental elements that control RNA metabolism properties that powerfully affect cancer biolog...
RNA Modifications in Cancer Biology
Through this Notice of Scientific Interest (NOSI), the National Cancer Institute intends to stimulate research on the role of RNA modifications in the area of cancer biology. Despite the recognitio...
The Role of RNA Modifications and RNA-modifying Proteins in Cancer Therapy and Drug Resistance
The advent of new genome-wide sequencing technologies has uncovered abnormal RNA modifications and RNA editing in a variety of human cancers. The discovery of reversible RNA N6-methyladenosine (RNA...
The emerging roles of METTL1-mediated tRNA m 7 G methylation in cancer development and immunotherapy
RNA modifications, particularly N7-methylguanosine (m7G), have emerged as critical epigenetic regulators in cancer biology. METTL1, a conserved S-adenosylmethionine-dependent methyltransferase, cat...
Latest Developments
Recent developments in RNA modifications and cancer research include the ongoing Keystone Symposia on RNA modifications held in March 2026, which focus on the biological functions and therapeutic potential of RNA modifications (keystonesymposia.org). Additionally, biotech companies like STORM Therapeutics and AlidaBio announced a strategic collaboration in January 2026 to develop cancer therapies targeting RNA modifications, specifically focusing on METTL3 inhibition and m6A dynamics in clinical samples (stormtherapeutics.com, ddw-online.com). Furthermore, research continues into the role of RNA methylation in cancer, with studies exploring m6A, m5C, and other modifications influencing tumor progression, drug resistance, and potential therapeutic targets (nature.com, feinberg.northwestern.edu, frontiersin.org) as of early 2026.
Sources
Frequently Asked Questions
What is m6A in RNA modifications and cancer?
m6A, or N6-methyladenosine, is the most prevalent internal RNA modification that controls RNA stability, translation, and metabolism. In cancer, m6A dysregulation involves writer, eraser, and reader proteins impacting oncogenesis. 'The epitranscriptome meets non-coding RNA: m6A-mediated regulation in oncogenesis and therapy' reviews its roles.
How do RNA-seq tools analyze modifications in cancer?
Tools like 'Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2' by Love et al. (2014) perform moderated estimation for differential expression tied to modifications. 'STAR: ultrafast universal RNA-seq aligner' by Dobin et al. (2012) handles spliced alignments for accurate read mapping. These enable quantification with 'featureCounts' by Liao et al. (2013).
What role does METTL1 play in cancer?
METTL1 methylates tRNA at m7G sites with cofactor WDR4, stabilizing tRNA and promoting cancer development. It regulates translation and immunotherapy responses. 'The emerging roles of METTL1-mediated tRNA m 7 G methylation in cancer development and immunotherapy' describes these functions.
What applications target RNA modifications in therapy?
STORM Therapeutics pioneers drugs reprogramming cells via RNA modifying enzymes for cancer. FTO demethylase reverses m6A, linked to drug resistance per 'The Role of RNA Modifications and RNA-modifying Proteins in Cancer Therapy and Drug Resistance'. NCI's NOSI funds research on these for biology insights.
How are RNA modifications mapped in cancer studies?
Tools like RNAmodR and RNAFramework detect post-transcriptional modifications from high-throughput sequencing data. NetRNApan uses deep learning for transcriptome-wide mapping. 'New SMART tool maps RNA modifications to tackle cancer' enables rapid high-throughput profiling.
What is the current state of RNA modification research in cancer?
Research shows substantial impacts on gene expression, with NCI stimulating mechanistic studies via NOSI. Preprints from 2026 detail m6A, m7G, and therapy roles. Field has 112,541 works, supported by RNA-seq pipelines like DESeq2 and STAR.
Open Research Questions
- ? How do dynamic RNA editing events mechanistically drive cancer-specific gene expression changes?
- ? What are the precise interactions between m6A erasers like FTO and drug resistance pathways in tumors?
- ? In what ways does METTL1-WDR4 complex dysregulation affect tRNA stability and immunotherapy efficacy?
- ? How can high-throughput tools improve resolution for detecting rare RNA modifications in heterogeneous cancers?
- ? What tissue- and cancer-specific signatures emerge from integrative analyses of RNA modification machinery?
Recent Trends
Preprints from early 2026 emphasize m6A regulation via epitranscriptome in oncogenesis and therapy, METTL1 m7G in cancer and immunotherapy, and FTO-linked drug resistance.
NCI issued NOSI on RNA modifications in cancer biology.
News covers STORM Therapeutics' RNA-modifying enzyme drugs and a SMART tool for modification mapping.
No 5-year growth rate available for 112,541 works.
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