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METTL3-mediated circ_0003998 serves as oncogene in non-small cell lung cancer through regulating miR-330-5p/CXCL3

Guanhua Liu1, Zhilong Li1, Chaowei Tang1

  • 1Thoracic Surgery Department, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.

Cell Cycle (Georgetown, Tex.)
|August 8, 2025
PubMed

Insights

Circular RNA circ_0003998 promotes non-small cell lung cancer (NSCLC) progression by regulating the miR-330-5p/CXCL3 axis. METTL3 enhances circ_0003998 expression via m6A modification, offering a potential therapeutic target for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) play a role in cancer development.
  • The specific role of circ_0003998 in non-small cell lung cancer (NSCLC) requires further investigation.

Purpose of the Study:

  • To elucidate the mechanism of circ_0003998 in NSCLC.
  • To investigate the regulatory pathway involving circ_0003998, microRNA-330-5p (miR-330-5p), and chemokine (C-X-C motif) ligand 3 (CXCL3).
  • To explore the role of methyltransferase-3 (METTL3) in circ_0003998 expression and its impact on NSCLC.

Main Methods:

  • Quantitative real-time PCR (RT-qPCR) and Western blot to assess gene and protein expression.
  • In vitro assays (proliferation, apoptosis, angiogenesis, migration, invasion) and in vivo animal experiments to evaluate circ_0003998 function.
  • Dual-luciferase reporter assays, RNA Immunoprecipitation (RIP), and methylated RNA Immunoprecipitation (MeRIP) to confirm molecular interactions.

Main Results:

  • Circ_0003998 was significantly upregulated in NSCLC tissues and cells.
  • Knockdown of circ_0003998 inhibited NSCLC cell proliferation, angiogenesis, migration, and invasion.
  • Circ_0003998 acted as a sponge for miR-330-5p, which targets CXCL3; this axis regulated NSCLC malignancy.
  • METTL3 promoted circ_0003998 expression through m6A modification.

Conclusions:

  • Circ_0003998 promotes NSCLC progression by modulating the miR-330-5p/CXCL3 axis.
  • METTL3-mediated upregulation of circ_0003998 contributes to NSCLC malignancy.
  • Circ_0003998 represents a potential therapeutic target for NSCLC treatment.
Keywords:
CXCL3Non-small cell lung cancercirc_0003998m6A methylationmiR-330-5p

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