EPITRANSCRIPTOMICS IN CANCER PROGRESSION 🎗️

“ℂ𝕝𝕠𝕟𝕒𝕝 𝕖𝕧𝕠𝕝𝕦𝕥𝕚𝕠𝕟 𝕚𝕤 𝕥𝕙𝕖 𝕖𝕟𝕘𝕚𝕟𝕖 𝕠𝕗 𝕔𝕒𝕟𝕔𝕖𝕣 𝕡𝕣𝕠𝕘𝕣𝕖𝕤𝕤𝕚𝕠𝕟; 𝕥𝕙𝕖 𝕥𝕦𝕞𝕠𝕣 𝕚𝕤 𝕟𝕠𝕥 𝕠𝕟𝕖 𝕖𝕟𝕥𝕚𝕥𝕪 𝕓𝕦𝕥 𝕒 𝕡𝕠𝕡𝕦𝕝𝕒𝕥𝕚𝕠𝕟 𝕠𝕗 𝕔𝕠𝕞𝕡𝕖𝕥𝕚𝕟𝕘 𝕔𝕝𝕠𝕟𝕖𝕤.” - Professor Peter Nowell (Emeritus)

🧬 Cancer remains a leading cause of morbidity & mortality worldwide, characterized by uncontrolled cell growth, invasion, and metastasis. Beyond genetic alterations, post-transcriptional regulation of RNA has emerged as a critical determinant of cancer biology. Epitranscriptomics, the study of chemical modifications on RNA, provides a dynamic layer of regulation influencing RNA stability, translation, & cellular localization.

🔹 Epitranscriptomic modifications include N6-methyladenosine (m6A), 5-methylcytidine (m5C), pseudouridine (Ψ), and RNA editing. These modifications are catalyzed by "writers" (e.g., methyltransferases), recognized by "readers," & reversed by "erasers" (demethylases), allowing fine-tuned responses to physiological and stress signals.

🔹 Among these, m6A is the most prevalent in eukaryotic mRNA & profoundly impacts cancer progression. Overexpression of the m6A writer METTL3 promotes tumor proliferation & poor prognosis, while reduced activity of demethylases like FTO is linked to malignancy progression. m6A modulates oncogene and tumor suppressor expression by affecting mRNA stability & translation, establishing a pro-tumorigenic environment.

🔹 Other modifications also contribute: m5C, mediated by NSUN2, supports aggressive phenotypes in cancers like glioblastoma. Pseudouridine stabilizes RNAs under stress, facilitating cancer cell survival. Collectively, these modifications demonstrate the broad epitranscriptomic regulation of tumor biology.

➡️ The tumor microenvironment (TME) shapes cancer progression and therapy response. RNA modifications influence cancer stroma interactions, including immune cell recruitment. For instance, m6A affects cytokine & chemokine expression, driving immune evasion or pro-tumor inflammation. Moreover, hypoxia; a common TME feature, modulates RNA modification machinery, enhancing tumor adaptation & therapy resistance.

➡️ Targeting RNA-modifying enzymes represents a promising strategy. Small molecules that inhibit m6A demethylases or enhance methyltransferase activity could suppress tumor growth. The reversibility of RNA modifications offers an advantage over permanent genetic alterations, enabling dynamic, precision-based interventions tailored to individual epitranscriptomic profiles.

⚠️ In an Oystershell, epitranscriptomics is a frontier in cancer research, revealing how RNA modifications, especially m6A, m5C, and pseudouridine, influence tumor behavior & TME interactions.

Abubakar Abubakar ✍🏻

• He, L., et al. (2019). Molecular Cancer, 18(1), 176.

• Shi et al, (2019). Molecular Cell, 74(4), 640-650.

#Epitranscriptomics #m6A #RNAmodifications #RNAResearch #TargetedTherapy #CRISPR #NGS ⚕️