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Updated: May 13, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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TNF-α inhibites non-small cell lung cancer cells proliferation by targeting THRIL in an FTO-YTHDF2-dependent manner

Yixin Dong1, Naihui Sun2, Yue Qiang1

  • 1Department of Pathogenbiology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.

Archives of Biochemistry and Biophysics
|May 1, 2025
PubMed

Insights

Tumor necrosis factor-alpha (TNF-α) inhibits non-small cell lung cancer (NSCLC) proliferation by decreasing THRIL expression. This pathway involves FTO, YTHDF2, and HuR, highlighting THRIL as a potential therapeutic target in NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Tumor necrosis factor-alpha (TNF-α) is a key cytokine in cancer progression, influencing tumor cell proliferation and survival.
  • The precise molecular mechanisms of TNF-α action in cancer, particularly non-small cell lung cancer (NSCLC), are not fully elucidated.
  • Long non-coding RNAs (lncRNAs) play critical roles in cancer development and progression.

Purpose of the Study:

  • To investigate the role of heterogenous nuclear ribonucleoprotein L related immunoregulatory LncRNA (THRIL) in non-small cell lung cancer (NSCLC).
  • To elucidate the regulatory feedback loop between TNF-α and THRIL in NSCLC.
  • To identify potential therapeutic targets and biomarkers for NSCLC.

Main Methods:

  • Analysis of THRIL expression in NSCLC cells and tissues.
  • Knockdown of THRIL to assess its impact on NSCLC cell proliferation and apoptosis.
  • Investigation of the molecular mechanisms involving TNF-α, FTO, YTHDF2, and HuR in regulating THRIL expression and stability.
  • Assessment of m6A methylation of THRIL transcripts.

Main Results:

  • High TNF-α concentration decreased THRIL expression, inhibiting NSCLC cell proliferation and promoting apoptosis.
  • THRIL expression was upregulated in NSCLC samples.
  • TNF-α reduced THRIL methylation by enhancing FTO, leading to YTHDF2-mediated degradation.
  • THRIL interacted with HuR to stabilize TNF-α mRNA, creating a feedback loop.

Conclusions:

  • TNF-α inhibits NSCLC proliferation through the FTO/YTHDF2/THRIL axis.
  • THRIL acts as a crucial regulator in the TNF-α-mediated response in NSCLC.
  • THRIL represents a promising biomarker and therapeutic target for NSCLC treatment.
Keywords:
FTOHuRNSCLCTHRILTNF-α

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