FOXM1 regulates radiosensitivity of lung cancer cell partly by upregulating KIF20A

Area of Science:

• Oncology
• Molecular Biology
• Radiotherapy Research

Background:

• Forkhead box protein M1 (FOXM1) is a key regulator in tumorigenesis.
• FOXM1 influences radiosensitivity in glioma and breast cancer.
• Lung cancer radiosensitivity mechanisms require further elucidation.

Purpose of the Study:

• To investigate FOXM1's role in human lung cancer radioresistance.
• To explore the molecular mechanisms underlying FOXM1's effect on radiotherapy resistance.

Main Methods:

• Analysis of FOXM1 and KIF20A expression in lung cancer cells (A549, H1299) post-ionizing radiation (IR).
• FOXM1 and KIF20A knockdown experiments to assess effects on cell survival, proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT).
• Reintroduction of KIF20A to validate its role in FOXM1-mediated radioresistance.

Main Results:

• FOXM1 expression increased in lung cancer cells after IR.
• FOXM1 inhibition reduced cell survival, proliferation, and EMT, while promoting apoptosis post-IR.
• KIF20A expression was upregulated by IR and downregulated by FOXM1 inhibition; KIF20A knockdown impaired cell survival.
• KIF20A reintroduction partially reversed FOXM1 inhibition effects on proliferation, apoptosis, and metastasis.

Conclusions:

• FOXM1 significantly contributes to radioresistance in human lung cancer.
• FOXM1 enhances radioresistance, potentially by inducing KIF20A expression.
• Targeting FOXM1 and KIF20A may offer novel therapeutic strategies for lung cancer radiotherapy.