2. Academic Validation
  3. PFOA exposure promotes prostate cancer progression by enhancing autophagy through m6A modification of MAPK15 mRNA

PFOA exposure promotes prostate cancer progression by enhancing autophagy through m6A modification of MAPK15 mRNA

  • Ecotoxicol Environ Saf. 2025 Aug 9:303:118839. doi: 10.1016/j.ecoenv.2025.118839.
Yongjing Qian 1,  Zixuan Liu 2,  Xinyi Lv 3,  Xiaojing Cai 4,  Jianfeng Wei 5,  Ling Zhang 6,  Xiannan Meng 7
Affiliations

Affiliations

  • 1 Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: qianyj0609@163.com.
  • 2 Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: liuzixuan61@163.com.
  • 3 Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: xinyi_lv322@163.com.
  • 4 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University), 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: 3399467588@qq.com.
  • 5 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University), 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: wjf@xzhmu.edu.cn.
  • 6 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University), 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: zhanglxy@xzhmu.edu.cn.
  • 7 Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: mengxiann@xzhmu.edu.cn.
PMID: 40784096 DOI: 10.1016/j.ecoenv.2025.118839
Abstract

Perfluorooctanoic acid (PFOA) is a globally pervasive environmental contaminant characterized by chemical stability and bioaccumulation through the food chain, posing serious health risks to both humans and Animals. Accumulating evidence has linked PFOA exposure to the development of various cancers, including prostate Cancer (PCa), renal Cancer, breast Cancer, and ovarian Cancer. However, the molecular mechanisms by which PFOA promotes PCa progression remain unclear. In this study, we demonstrate that low-dose PFOA exposure enhances the expression of mitogen-activated protein kinase 15 (MAPK15), thereby promoting Autophagy and facilitating tumor cell proliferation. Mechanistically, PFOA binds to the N6-methyladenosine (m6A) demethylase FTO (fat mass and obesity-associated protein), inhibiting its demethylase activity and resulting in elevated m6A modification levels on MAPK15 mRNA. This modification leads to increased MAPK15 protein expression, which in turn activates Autophagy pathways and drives the proliferation, migration, and invasion of PCa cell lines. Collectively, our findings provide critical molecular evidence for the carcinogenic potential of PFAS compounds and offer new insights into environmental toxicology and ecological risk assessment.

Keywords

N6-methyladenosine (m(6)A) and autophagy; Perfluorooctanoic acid (PFOA); Prostate cancer (PCa).

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