Article Alert: A Mechanistic Basis for Heat Therapy Against HPV Malignancies

Human Papillomavirus (HPV) is responsible for almost all cervical cancers as well as many other anogenital neoplasms. Though several HPV vaccines have been developed, effective therapies are still needed. In an intriguing study, Wang et al. report that the mRNA of the pivotal viral oncoprotein early protein 7 (E7) is modified in HPV-infected cells by N⁶-methyladenosine (m⁶A) (via the METTL3/METTL14 complex) and stabilized by binding to the m⁶A reader IGF2BP1. The authors use a range of techniques, including both mouse and zebrafish models, to show that heat treatment leads to downregulation of both components of the mRNA-reader protein oncogenic complex (with IGF2BP1 forming granules that are degraded by ubiquitin-proteasome activity) and inhibition of the tumorigenic propensity of HPV-infected cells. In addition to augmenting the considerable literature supporting use of heat therapy against some cancers, this study also importantly reveals the molecular mechanism underlying the surprising mutual regulation between the m6A-modified E7 mRNA and its protein reader IGF2BP1.

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