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

Shuai Xu1,2, Xiaolin Gao2, Jianqing Qiu2

  • 1Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.

Aging
|February 21, 2023
PubMed
Abstract

Insights

Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is downregulated in epithelial ovarian cancer (EOC). Restoring TIPE2 suppresses EOC growth by inhibiting the PI3K/Akt pathway and influences immune cell infiltration.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Epithelial ovarian cancer (EOC) remains a leading cause of cancer-related death among gynecologic malignancies.
  • The precise etiology of EOC is not fully understood.
  • Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a key regulator of inflammation and immune homeostasis implicated in various cancers.

Purpose of the Study:

  • To investigate the role and regulatory mechanisms of TIPE2 in epithelial ovarian cancer (EOC).
  • To explore the correlation between TIPE2 expression and tumor immune infiltration in the ovarian cancer microenvironment.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and Western blot to assess TIPE2 expression in EOC tissues and cell lines.
  • In vitro assays (proliferation, colony formation, transwell, apoptosis) to evaluate TIPE2 function.
  • RNA-sequencing, western blot, and bioinformatics analyses (CIBERSORT, TISCH, TIMER, TISIDB, GEPIA) to elucidate molecular mechanisms and immune infiltration.

Main Results:

  • TIPE2 expression was significantly reduced in EOC samples and cell lines.
  • Overexpression of TIPE2 inhibited EOC cell proliferation, colony formation, and motility.
  • TIPE2 suppressed EOC progression by blocking the PI3K/Akt signaling pathway, with partial abrogation by a PI3K agonist.
  • TIPE2 expression correlated positively with immune cell infiltration and may regulate macrophage polarization.

Conclusions:

  • TIPE2 acts as a tumor suppressor in EOC by inhibiting proliferation, motility, and blocking the PI3K/Akt pathway.
  • TIPE2 influences the tumor microenvironment by correlating with immune cell infiltration.
  • TIPE2 represents a potential therapeutic target for ovarian cancer treatment.
Keywords:
PI3K/Akt signaling pathwayTIPE2epithelial ovarian cancerprogressiontumor microenvironment

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