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IRF4 Enhances Radiosensitivity of Cervical Cancer by Inhibiting the PI3K/Akt/mTOR Pathway to Regulate Autophagy

Meihui Gao1, Zhaolei Cui2, Huachun Song3

  • 1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.

Cancer Science
|January 19, 2026
PubMed

Insights

Interferon regulatory factor 4 (IRF4) is decreased in cervical cancer, suppressing tumor growth and enhancing radiosensitivity. IRF4 promotes autophagy via the PI3K/Akt/mTOR pathway, offering a potential therapeutic target for improving radiotherapy outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cervical cancer remains a significant global health challenge.
  • The precise role of Interferon regulatory factor 4 (IRF4) in cervical cancer pathogenesis is not well understood.
  • Identifying novel therapeutic targets is crucial for improving treatment efficacy.

Purpose of the Study:

  • To investigate the biological role of IRF4 in cervical cancer.
  • To determine the effect of IRF4 on cervical cancer progression and radiosensitivity.
  • To elucidate the underlying molecular mechanisms, including its impact on autophagy and the PI3K/Akt/mTOR pathway.

Main Methods:

  • Immunohistochemistry, immunoblotting, CCK-8 assays, EdU incorporation, clonogenic survival assays, flow cytometry, transmission electron microscopy, immunofluorescence, and heterotopic transplantation models.
  • Overexpression of IRF4 in cervical cancer cell lines (Siha and HeLa).
  • Inhibition of the PI3K/Akt/mTOR pathway and induction of autophagy.

Main Results:

  • IRF4 expression was significantly downregulated in cervical cancer tissues and cell lines compared to normal controls.
  • IRF4 overexpression inhibited cervical cancer cell proliferation, migration, and invasion.
  • IRF4 enhanced radiosensitivity by upregulating autophagy-related proteins (LC3, Beclin-1), promoting autophagosome formation, and downregulating P62 through PI3K/Akt/mTOR pathway inhibition.
  • In vivo studies confirmed IRF4's role in augmenting tumor response to radiation, with synergistic effects observed when combined with rapamycin.

Conclusions:

  • IRF4 acts as a tumor suppressor in cervical cancer.
  • IRF4 enhances radiosensitivity by modulating autophagy via the PI3K/Akt/mTOR pathway.
  • IRF4 represents a promising therapeutic target for improving cervical cancer radiotherapy outcomes.
Keywords:
autophagycervical cancerinterferon regulatory factor 4radiosensitivity

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