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Circ_0060927 regulates miR-331-3p/ERK/MAPK pathway reaction in non-small cell lung cancer through METTL14-driven

Yang Liao1, Ji Song2, Chun Luo1

  • 1Department of Pulmonary and Critical Care Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, China.

Frontiers in Oncology
|December 1, 2025
PubMed
Abstract

Insights

Circular RNAs (circRNAs) like circ_0060927 promote non-small cell lung cancer (NSCLC) progression by interacting with miR-331-3p and influencing the ERK/MAPK pathway. This highlights circRNA methylation as a potential therapeutic target for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-coding RNAs, particularly circular RNAs (circRNAs), are critical genetic regulators implicated in tumor development.
  • Circular RNAs, specifically circ_0060927, are investigated for their role in modulating non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • To elucidate the influence of circ_0060927 on NSCLC progression.
  • To investigate the regulatory mechanisms, including m6A methylation, underlying circ_0060927's function in NSCLC.

Main Methods:

  • Gene expression (circ_0060927, MAP2K7, METTL14, ERK, p-ERK, p38MAPK, p-p38MAPK) analyzed using RT-qPCR and Western Blot.
  • RNA immunoprecipitation (RIP-RT-qPCR) to assess m6A methylation of circ_0060927.
  • Functional assays (Cell Counting Kit-8, apoptosis, wound healing, Transwell) evaluated NSCLC cell proliferation, motility, and apoptosis.

Main Results:

  • NSCLC cells (L78, A549) exhibited elevated circ_0060927 expression and m6A methylation.
  • Circ_0060927 promoted NSCLC cell proliferation and motility while reducing apoptosis, dependent on METTL14-mediated m6A methylation.
  • Circ_0060927 targeted miR-331-3p, which in turn suppressed NSCLC via the ERK/MAPK pathway by affecting MAP2K7 expression.

Conclusions:

  • Circ_0060927 promotes NSCLC malignancy through miR-331-3p interaction.
  • MiR-331-3p acts as an NSCLC inhibitor by targeting the ERK/MAPK pathway via MAP2K7.
  • Findings offer insights into NSCLC molecular mechanisms and the therapeutic potential of circRNA methylation.
Keywords:
ERK/MAPK signaling axisNSCLCcirc_0060927m6A methylationmiR-331-3p

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