AI Article Synopsis

  • E7 protein from HPV is crucial for cancer development, making it a key target for treatment.
  • Heat treatment can specifically destabilize the E7 mRNA oncotranscript complex, reducing its levels in HPV-infected cells.
  • This method works by promoting the aggregation of IGF2BP1, which binds to the modified E7 mRNA, and ultimately helps reverse HPV-related cancer in lab settings.

Article Abstract

Human papillomavirus (HPV)-induced carcinogenesis critically depends on the viral early protein 7 (E7), making E7 an attractive therapeutic target. Here, we report that the E7 messenger RNA (mRNA)-containing oncotranscript complex can be selectively targeted by heat treatment. In HPV-infected cells, viral E7 mRNA is modified by N-methyladenosine (mA) and stabilized by IGF2BP1, a cellular mA reader. Heat treatment downregulates E7 mRNA and protein by destabilizing IGF2BP1 without the involvement of canonical heat-shock proteins and reverses HPV-associated carcinogenesis in vitro and in vivo. Mechanistically, heat treatment promotes IGF2BP1 aggregation only in the presence of mA-modified E7 mRNA to form distinct heat-induced mA E7 mRNA-IGF2BP1 granules, which are resolved by the ubiquitin-proteasome system. Collectively, our results not only show a mutual regulation between mA RNA and its reader but also provide a heat-treatment-based therapeutic strategy for HPV-associated malignancies by specifically downregulating E7 mRNA-IGF2BP1 oncogenic complex.

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http://dx.doi.org/10.1016/j.celrep.2022.111546DOI Listing

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