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Aberrant CircTMEM45A Facilitates Inflammatory Progression of Esophageal Squamous Cell Carcinoma through m5C-Mediated

Lingjiao Meng1,2, Haotian Wu3,4, Jiaxiang Wu3,4

  • 1Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Cancer Research
|April 11, 2025
PubMed

Insights

Circular RNA circTMEM45A promotes esophageal squamous cell carcinoma (ESCC) progression by activating inflammatory pathways. Targeting circTMEM45A may offer new diagnostic and therapeutic strategies for ESCC patients.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Esophageal cancer lacks effective treatments due to limited understanding of its mechanisms.
  • Epigenetic alterations, including 5-methylcytosine (m5C) modification and circular RNA (circRNA) expression, are implicated in cancer development.

Purpose of the Study:

  • To investigate the role of circTMEM45A in esophageal squamous cell carcinoma (ESCC).
  • To elucidate the molecular mechanisms underlying circTMEM45A's function in ESCC progression.

Main Methods:

  • Quantitative analysis of circTMEM45A expression in ESCC tissues.
  • In vitro and in vivo functional assays to assess circTMEM45A's impact on ESCC.
  • RNA immunoprecipitation and Western blot assays to identify interacting proteins and molecular pathways.

Main Results:

  • circTMEM45A was upregulated in ESCC tissues and correlated with advanced stages and poor survival.
  • Elevated circTMEM45A promoted ESCC cell proliferation, migration, and invasion.
  • circTMEM45A activated the NLRP3/caspase 1/IL-1β pathway by interacting with NSUN2, ALYREF, and YBX1.
  • circTMEM45A further enhanced the IL-1β/IL1R1 pro-inflammatory cascade by stabilizing IL1B and IL1R1 mRNAs.

Conclusions:

  • circTMEM45A plays a crucial role in ESCC progression by modulating epigenetic modifications and activating inflammatory responses.
  • The interplay between circRNA and m5C modification drives tumorigenesis in ESCC.
  • circTMEM45A represents a promising diagnostic biomarker and therapeutic target for ESCC.

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