Academic Journal
FAM72A Knockdown Drives Cell Mitophagy and Pyroptosis in Ovarian Cancer Via the PINK1/Parkin Pathway.
| Τίτλος: | FAM72A Knockdown Drives Cell Mitophagy and Pyroptosis in Ovarian Cancer Via the PINK1/Parkin Pathway. |
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| Συγγραφείς: | Tan S; Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, No. 31 Guanghui Road, Zhengxiang District, Hengyang City, Hunan, 421000, China., Wang L; Department of Gynecology, Tongren People's Hospital, Tongren, Guizhou, 5543000, China., Xu Z; Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, No. 31 Guanghui Road, Zhengxiang District, Hengyang City, Hunan, 421000, China., Tang R; Department of Gynecology, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan Province, 421000, China., Xie W; Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, No. 31 Guanghui Road, Zhengxiang District, Hengyang City, Hunan, 421000, China. f_199901@163.com. |
| Πηγή: | Applied biochemistry and biotechnology [Appl Biochem Biotechnol] 2026 Aug; Vol. 198 (8), pp. 6193-6214. Date of Electronic Publication: 2026 May 20. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Humana Press Country of Publication: United States NLM ID: 8208561 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0291 (Electronic) Linking ISSN: 02732289 NLM ISO Abbreviation: Appl Biochem Biotechnol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Clifton, N.J. : Humana Press, c1981- |
| Ιατρικοί όροι (MeSH): | Pyroptosis*/genetics , Mitophagy*/genetics , Protein Kinases*/metabolism , Protein Kinases*/genetics , Ovarian Neoplasms*/metabolism , Ovarian Neoplasms*/pathology , Ovarian Neoplasms*/genetics , Ubiquitin-Protein Ligases*/metabolism , Ubiquitin-Protein Ligases*/genetics , Neoplasm Proteins*/metabolism , Neoplasm Proteins*/genetics , Gene Knockdown Techniques* , Signal Transduction*, Mitochondria/metabolism ; Female ; Humans ; PTEN-Induced Putative Kinase ; Animals ; Cell Line, Tumor ; Mice ; Mice, Nude |
| Περίληψη: | This study explored the role of Family with Sequence Similarity 72 Member A (FAM72A) in regulating mitophagy and pyroptosis via the PINK1/Parkin pathway in ovarian cancer (OC). Bioinformatics analysis and clinical tissue and cell assays revealed that FAM72A was significantly overexpressed in OC. Silencing FAM72A in OC cells suppressed proliferation, invasion, and migration, while promoting apoptosis. Additionally, FAM72A knockdown increased mitochondrial ROS levels, autophagosome-mitochondria colocalization, and the LC3II/I ratio and reduced p62 expression, mitochondrial membrane potential, and ATP levels in OC cells. Downregulation of FAM72A upregulated PINK1 and Parkin expression and increased the expression of pyroptosis-related markers including NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 in OC cells. Furthermore, the inhibitory effect of FAM72A knockdown was reversed by treating cells with mitochondrial inhibitors or by specifically knocking down PINK1. In vivo experiments confirmed that FAM72A promoted tumor growth by inhibiting the PINK1/Parkin pathway. Conclusively, FAM72A knockdown drives mitophagy and pyroptosis in OC by activating the PINK1/Parkin pathway, highlighting its potential as a therapeutic target for OC. (© 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
| Competing Interests: | Declarations. Ethical approval and consent to participate: Written informed consent was supplied by all participants. This study was conducted as per the Declaration of Helsinki, with ratification from the Ethics Committee of Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital. All animals underwent a one-week acclimatization period before the experiments. All animal experiments were carried out with ratification from the Institutional Animal Care and Use Committee of Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital.(Approval No.2024-63). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. |
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| Grant Information: | Grant No: 2025JJ80598 the Natural Science Foundation of Hunan Province |
| Contributed Indexing: | Keywords: FAM72A; Mitophagy; Ovarian cancer; PINK1/Parkin pathway; Pyroptosis |
| Substance Nomenclature: | EC 2.7.- (Protein Kinases) EC 2.3.2.27 (parkin protein) EC 2.3.2.27 (Ubiquitin-Protein Ligases) EC 2.7.11.1 (PTEN-Induced Putative Kinase) 0 (Neoplasm Proteins) |
| Entry Date(s): | Date Created: 20260520 Date Completed: 20260727 Latest Revision: 20260727 |
| Update Code: | 20260727 |
| DOI: | 10.1007/s12010-026-05718-6 |
| PMID: | 42159844 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1559-0291 |
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| DOI: | 10.1007/s12010-026-05718-6 |