مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Epitranscriptomic Modifications and Anoikis Resistance in Virus-associated Cancers
Epitranscriptomic Modifications and Anoikis Resistance in Virus-associated Cancers
Ehsan Kakavandi,1,*Mohammad Shayestehpour,2
1. Reference health laboratory, Deputy of Health, Isfahan University of Medical Sciences, Isfahan, Iran.
Introduction: Anoikis is a process of cell death, and anoikis resistance is one of the features of metastatic cancer cells that allows them to survive even when they lose attachment to the extracellular matrix (ECM), thus leading to invasiveness and metastasis. A number of oncoviruses like Epstein–Barr virus (EBV), hepatitis B virus (HBV), human papillomavirus (HPV), and human T-cell leukemia virus (HTLV) are implicated in the development and progression of human cancer. Meanwhile, epitranscriptomics, an emerging branch of epigenetics, has shown that chemical modifications of RNA molecules—particularly viral RNAs—can influence cell proliferation, immune evasion, and cell signaling pathways. The connection between viral epitranscriptomics and anoikis resistance is not well studied. This paper will discuss how epitranscriptomic marks on viral RNAs can induce anoikis resistance and oncogenesis. Ongoing studies extend our earlier manuscript, "Anoikis Resistance and Oncoviruses", by incorporating new epitranscriptomic profiling advances. Extending the background research of that paper, we here discuss how chemical modifications of viral RNAs can further impact anoikis resistance mechanisms in cancer cells.
Methods: The essay relies on peer-reviewed articles published between 2015 and 2025, focusing particularly on research articles that investigate RNA modifications in oncoviruses, the mechanisms of anoikis resistance in virus-associated cancers, and the applications of high-throughput mapping methods, such as MeRIP-seq and nanopore RNA sequencing. Relevant articles were identified by PubMed, Scopus, and Web of Science searching using terms like "epitranscriptomics," "anoikis," "oncovirus," "m6A," and "cancer metastasis." Articles were selected based on relevance, novelty, and methodological quality, with particular interest in those linking viral RNA modifications to epithelial–mesenchymal transition (EMT), integrin signaling, and regulation of apoptosis.
Results: Recent studies have shown that viral RNA modifications—specifically N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ)—stabilize oncogenic transcripts and control host cell physiology to a significant extent. For instance, m6A marks on HPV transcripts promote translation of E6/E7 oncogenes by recruitment of YTHDF1 and IGF2BP1, which stabilize mRNA and recruit ribosomes. These oncogenes inactivate p53 and Rb pathways, granting EMT and anoikis resistance. EBV RNAs, including EBERs and BART miRNAs, are often m6A/m5C modified to control integrin signaling by ITGA5 upregulation and FAK phosphorylation activation. It promotes cytoskeleton remodeling and detachment survival and suppresses TLR-mediated immune response. In HBV, methylation of HBx transcript at m6A stabilizes HBx transcripts and promotes anti-apoptotic signaling through Bcl-2 and survivin. HTLV is also observed to commandeer host METTL3/METTL14 complexes to alter Tax covalently and HBZ RNAs, preventing caspase-3 activation and anchorage-independent growth. Together, these epitranscriptomic processes promote viral persistence, immune evasion, and metastatic progression in virus-associated cancers, and place RNA modifications as actionable targets.
Conclusion: Viral epitranscriptomics represents a new and underexplored dimension of viral-associated cancer biology with particular consideration of anoikis resistance. The ability of oncoviruses to regulate RNA modifications may be central to how they promote metastasis and immune evasion. Additional research integrating transcriptomic profiling with functional assays will be required to shed light on these interactions and uncover novel therapeutic targets. Additional knowledge of this axis may pave the way for biomarker discovery and precision medicine strategies for virus-associated cancers.