NLRC3 Inhibits the Migration and Invasion of Adenomyosis by Modulating the PI3K/AKT/mTOR Pathway in Endometrial Cells

Critical Reviews™ in Immunology Published 6 issues per year ISSN Print: 1040-8401 ISSN Online: 2162-6472 Research Article NLRC3 Inhibits the Migration and Invasion of Adenomyosis by Modulating the PI3K/AKT/mTOR Pathway in Endometrial Cells ABSTRACT Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemical (IHC) staining were used to assess the expression of NLRC3 in tissues and cells. The effects of NLRC3 on the proliferation, apoptosis, migration, and invasion of endometrial cells were investigated via Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, cell scratch and transwell assays, respectively. The mouse model of adenomyosis was constructed. The regulation mechanisms by which NLRC3 acts were further verified in vivo study. The study revealed epithelial-mesenchymal transition (EMT) related protein expression was upregulated and NLRC3 was downregulated in endometria of patients with adenomyosis. Upregulation of NLRC3 expression reduced endometrial cell growth, migration, invasion, and promoted cell apoptosis rate. Mechanistically, upregulation of NLRC3 expression inhibited the level of EMT and blocked the PI3K/AKT/mTOR pathway activation in endometrial cells. In vivo, increased the expression of NLRC3 decreased the levels of cytokines (IL-6 and IL-8), inhibited the levels of PI3K/AKT/mTOR pathway related genes and mitigated disease severity. Our findings indicate that NLRC3 inhibits migration and invasion of adenomyosis by modulating PI3K/AKT/mTOR pathway in endometrial cells. Consequently, NLRC3 holds promise as a potential therapeutic target for adenomyosis management. Figures - Struble J, Reid S, Bedaiwy MA. Adenomyosis: A clinical review of a challenging gynecologic condition. J Minim Invasive Gynecol. 2016;23(2):164-85. - Hashimoto A, Iriyama T, Sayama S, Okamura A, Kato K, Fujii T, Kubota K, Ichinose M, Sone K, Kumasawa K, Nagamatsu T, Hirota Y, Osuga Y. 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