Position: RNA sidekick
Employer: MYC, a famously overcaffeinated gene regulator
Responsibilities: Slip into enhancers, boost nearby genes, encourage tumor growth, make biologists mutter "well, that is inconvenient" into their coffee.
That, give or take some molecular spelling, is the vibe of a new paper on MYC-bound enhancer RNAs, or eRNAs. The study asks a sneaky question: what if MYC, one of cancer biology's most notorious troublemakers, is not just bossing DNA around, but also teaming up with little noncoding RNAs that help it do the job better? According to this work, the answer is yes - and the partnership looks especially relevant in cancer (Li et al., 2026).
Tiny notes passed in the back of the genome
First, the cast.
MYC is a transcription factor, meaning it helps control which genes get turned on. In a lot of cancers, MYC is overactive. That is bad news because MYC tends to favor growth, division, and the general cellular attitude of "what if we ignored the speed limit."
Enhancers are stretches of DNA that act like long-distance hype crews for genes. They can sit far away from a gene in the linear genome, then loop over in 3D space and help crank up transcription. And active enhancers often make short RNA molecules called enhancer RNAs, or eRNAs. For years, those RNAs had a reputation somewhere between "important regulator" and "molecular background chatter." Biology loves that kind of ambiguity. It is basically the genre.
This new paper pushes eRNAs closer to the "actually doing something" camp. The authors integrated several kinds of genomic data and found that MYC broadly binds eRNAs across cancer cell lines and tumors. These eRNAs were notably cancer- and tissue-specific, which is exactly the sort of detail that makes cancer biologists lean forward in their chairs.
The plot twist: MYC may need a local guide
The headline finding is not just that MYC touches eRNAs. It is that some of these RNAs seem to help MYC regulate genes in cis, meaning near the place where the RNA is made.
The team built a computational pipeline to predict which MYC-bound eRNAs might control nearby target genes, then backed many of those predictions with chromatin interaction data. Translation: they did not just point at a suspicious RNA and yell "accomplice." They checked whether the enhancer and gene were actually talking in 3D.
Then they zoomed in on one eRNA in breast cancer, which they named MERG1. MERG1 appears to help MYC increase its occupancy at the GREB1 promoter, which in turn boosts chromatin remodeling and gene activation. GREB1 is already known in hormone-responsive breast cancer circles, so this is not some random genomic shrub. It is a meaningful plant in the garden.
When the researchers disrupted MERG1, tumor-promoting behavior dropped. Even more interesting, antisense oligonucleotides delivered by nanoparticles reduced MYC-driven breast cancer growth in their models (Li et al., 2026). That is still preclinical, not a pharmacy shelf moment, but it is a very different sentence from "we found a weird RNA and then everybody went home."
Why this matters more than another weird RNA paper
Cancer research has a recurring problem: MYC is important, but hard to drug directly. It is one of those proteins that acts like it knows the police cannot quite get a grip on it. So researchers keep looking for vulnerabilities around it - its partners, its dependencies, its favorite furniture.
That is where this study gets interesting. It suggests MYC may rely on specific local RNAs to lock in certain cancer-driving programs. If that holds up, the field gets a more precise way to interfere. Not "turn off all transcription and hope for the best," but "quiet this one dangerous conversation."
That idea also fits with recent work showing that MYC can directly regulate enhancer activity and enhancer transcription, helping drive cancer-type-specific gene programs through RNA polymerase II and chromatin modifiers such as BRD4 and GCN5 (Jakobsen et al., 2024). Broader reviews and cancer studies have also argued that eRNAs are not genomic confetti. They can shape transcription, chromatin state, immune context, prognosis, and maybe therapy response (Napoli et al., 2022; Lewis et al., 2022; Zhang et al., 2025; Zhao et al., 2023).
The catch, because biology always sends one
There are still some speed bumps the size of small moons.
eRNAs are often short-lived and context-specific, which makes them tricky to study. It is also hard to prove whether the RNA molecule itself is doing the work, or whether the act of transcribing the enhancer is the real driver. This paper makes a solid case for MERG1 as a functional player, but one well-characterized example is not the same thing as a universal rulebook.
And while antisense approaches are exciting, delivering them safely and consistently to tumors is its own saga. Cancer cells are not known for being cooperative recipients of molecular mail.
Still, this is the kind of study that makes the noncoding genome feel less like a dark attic and more like a control room with a lot of unlabeled switches. MYC, apparently, has been pressing some of them with RNA-covered fingers.
References
Li S, Wang Z, Nguyen P, et al. MYC-bound enhancer RNAs in cis regulate gene transcription and tumorigenesis. Science Advances. 2026;12(17):eaeb5147. DOI: 10.1126/sciadv.aeb5147. PubMed: 42030388. PMCID: PMC13108557
Jakobsen ST, Jensen RAM, Madsen MS, et al. MYC activity at enhancers drives prognostic transcriptional programs through an epigenetic switch. Nature Genetics. 2024;56:663-674. DOI: 10.1038/s41588-024-01676-z
Napoli S, Munz N, Guidetti F, Bertoni F. Enhancer RNAs (eRNAs) in Cancer: The Jacks of All Trades. Cancers (Basel). 2022;14(8):1978. DOI: 10.3390/cancers14081978. PMCID: PMC9030334
Lewis MW, Wisniewska K, King CM, et al. Enhancer RNA Transcription Is Essential for a Novel CSF1 Enhancer in Triple-Negative Breast Cancer. Cancers (Basel). 2022;14(7):1852. DOI: 10.3390/cancers14071852. PMCID: PMC8997997
Zhang R, Chen Z, Li T, et al. Enhancer RNA in cancer: identification, expression, resources, relationship with immunity, drugs, and prognosis. Briefings in Functional Genomics. 2025;24:elaf007. DOI: 10.1093/bfgp/elaf007. PMCID: PMC12031722
Zhao H, Zhang C, Bo L, et al. Comprehensive identification and potential application of genetic alteration-driven enhancer RNAs for eRNA-targeted therapy in breast cancer. Genes & Diseases. 2023;11(5):101124. DOI: 10.1016/j.gendis.2023.101124. PMCID: PMC11167238
Disclaimer: The image accompanying this article is for illustrative purposes only and does not depict actual experimental results, data, or biological mechanisms.