TIPE2 acts as a tumor suppressor and correlates with tumor microenvironment immunity in epithelial ovarian cancer.

Background: Epithelial ovarian cancer (EOC) is one of the deadliest gynecologic cancers. The etiology of EOC has still not been elucidated thoroughly. Tumor necrosis factor--induced protein 8-like2 (TNFAIP8L2, TIPE2), an important regulator of inflammation and immune homeostasis, plays a critical role in the progression of various cancers. This study aims to investigate the role of TIPE2 in EOC.

Methods: Expression of TIPE2 protein and mRNA in EOC tissues and cell lines was examined using Western blot and quantitative real-time PCR (qRT-PCR). The functions of TIPE2 in EOC were investigated by cell proliferation assay, colony assay, transwell assay, and apoptosis analysis . To further investigate the regulatory mechanisms of TIPE2 in EOC, RNA-seq and western blot were performed. Finally, the CIBERSORT algorithm and databases including Tumor Immune Single-cell Hub (TISCH), Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction (TISIDB), and The Gene Expression Profiling Interactive Analysis (GEPIA) were used to elucidate its potential role in regulating tumor immune infiltration in the tumor microenvironment (TME).

Results: TIPE2 expression was shown to be considerably lower in both EOC samples and cell lines. Overexpression of TIPE2 suppressed EOC cell proliferation, colony formation, and motility . Mechanistically, TIPE2 suppressed EOC by blocking the PI3K/Akt signaling pathway, according to bioinformatics analysis and western blot in TIPE2 overexpression EOC cell lines, and the anti-oncogenic potentials of TIPE2 in EOC cells could be partially abrogated by the PI3K agonist, 740Y-P. Finally, TIPE2 expression was positively associated with various immune cells and possibly involved in the regulation of macrophage polarization in ovarian cancer.

Conclusions: We detail the regulatory mechanism of TIPE2 in EOC carcinogenesis, as well as how it correlates with immune infiltration, emphasizing its potential as a therapeutic target in ovarian cancer.