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m6A-modified circSTX6 as a key regulator of cervical cancer malignancy via SPI1 and IL6/JAK2/STAT3 pathways

Xiaotian Han1,2, Lingfang Xia1,2, Yong Wu1,2

  • 1Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Oncogene
|January 15, 2025
PubMed

Insights

Newly identified circSTX6 is highly expressed in cervical cancer (CC), promoting tumor growth and metastasis. It stabilizes SPI1, activating the JAK2/STAT3 pathway, and forms a feedback loop with METTL3, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers.
  • The specific functions of many newly discovered circRNAs, including in cervical cancer (CC), require further elucidation.
  • Understanding novel circRNAs is crucial for advancing CC research and therapy.

Purpose of the Study:

  • To investigate the expression and oncogenic potential of a novel circRNA, circSTX6, in cervical cancer.
  • To elucidate the molecular mechanisms underlying circSTX6's function in CC progression.
  • To identify potential therapeutic targets for cervical cancer based on circSTX6's role.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess circSTX6 expression levels in CC tissues and cell lines.
  • Cell-based assays to evaluate the effects of circSTX6 on cell survival, proliferation, invasion, and migration.
  • Western blotting and luciferase reporter assays to investigate the interaction between circSTX6, SPI1, IL6, and the JAK2/STAT3 pathway.
  • RNA immunoprecipitation (RIP) and m6A RNA immunoprecipitation (m6A-RIP) assays to confirm molecular interactions and modifications.

Main Results:

  • circSTX6 expression is significantly upregulated in cervical cancer tissues and correlates with poor patient prognosis.
  • Overexpression of circSTX6 promotes cell survival, proliferation, invasion, and migration in CC cells.
  • circSTX6 enhances SPI1 stability, leading to increased IL6 transcription and activation of the JAK2/STAT3 signaling pathway.
  • METTL3-mediated m6A modification stabilizes circSTX6, which is recognized by YTHDC1, establishing a positive feedback loop involving METTL3, circSTX6, and SPI1.

Conclusions:

  • circSTX6 acts as an oncogenic circRNA in cervical cancer by promoting tumor progression through the SPI1/IL6/JAK2/STAT3 axis.
  • A positive feedback loop involving METTL3, circSTX6, and SPI1 contributes to the oncogenic functions of circSTX6.
  • circSTX6 represents a promising novel biomarker and therapeutic target for cervical cancer molecular therapies.

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