IMR Press / FBL / Volume 29 / Issue 5 / DOI: 10.31083/j.fbl2905189
Open Access Original Research
Exosomal EGFR and miR-381-3P Mediate HPV-16 E7 Oncoprotein-Induced Angiogenesis of Non-Small Cell Lung Cancer
Riming Zhan1,2,3,†Hua Yu1,2,†Guihong Zhang1,2Qingkai Ding1,2Huan Li1,2Xiangyong Li1,2,4,5Xudong Tang1,2,4,5,*
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1 Institute of Biochemistry and Molecular Biology, School of Basic Medicine, Guangdong Medical University, 524023 Zhanjiang, Guangdong, China
2 Collaborative Innovation Center for Antitumor Active Substance Research and Development, School of Basic Medicine, Guangdong Medical University, 524023 Zhanjiang, Guangdong, China
3 Department of Blood Transfusion, Affiliated Hospital of Guangdong Medical University, 524001 Zhanjiang, Guangdong, China
4 Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, 523808 Dongguan, Guangdong, China
5 Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Medical University, 523808 Dongguan, Guangdong, China
*Correspondence:; (Xudong Tang)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2024, 29(5), 189;
Submitted: 30 November 2023 | Revised: 25 March 2024 | Accepted: 8 April 2024 | Published: 15 May 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: It has been demonstrated that exosomes derived from HPV-16 E7-over-expressiong non-small cell lung cancer (NSCLC) cells (E7 Exo) trigger increased levels of epidermal growth factor receptor (EGFR) and miR-381-3p. The purpose of this investigation was to examine the role of E7 Exo in NSCLC angiogenesis, and to analyze the contribution of exosomal EGFR and miR-381-3p to it. Methods: The influence of E7 Exo on the proliferation and migration of human umbilical vein endothelial cells (HUVECs) was assessed using colony formation and transwell migration assays. Experiments on both cells and animal models were conducted to evaluate the angiogenic effect of E7 Exo treatment. The involvement of exosomal EGFR and miR-381-3p in NSCLC angiogenesis was further investigated through suppressing exosome release or EGFR activation, or by over-expressing miR-381-3p. Results: Treatment with E7 Exo increased the proliferation, migration, and tube formation capacities of HUVECs, as well as angiogenesis in animal models. The suppression of exosome release or EGFR activation in NSCLC cells decreased the E7-induced enhancements in HUVEC migration and tube formation, and notably reduced vascular endothelial growth factor A (VEGFA) and Ang-1 levels. HUVECs that combined miR-381-3p mimic transfection and E7 Exo treatment exhibited a more significant tube-forming capacity than E7 Exo-treated HUVECs alone, but were reversed by the miR-381-3p inhibitor. Conclusion: The angiogenesis induced by HPV-16 E7 in NSCLC is mediated through exosomal EGFR and miR-381-3p.

HPV-16 E7
2022KTSCX048/Characteristic Innovation Project of Guangdong Province Ordinary University (Nature Science)
Fig. 1.
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