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RNA-Binding Proteins MCPIP3 and IGF2BP3 Antagonize Lung Cancer Metastasis by Reversibly Regulating METAP2 Expression

Shaoyu Song1, Hongwei Li1, Ailing Li1

  • 1Institute of Microcirculation, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.

Cancers
|August 13, 2026
PubMed

Insights

MCPIP3 and IGF2BP3 RNA-binding proteins antagonistically regulate lung adenocarcinoma (LUAD) metastasis by controlling METAP2 mRNA stability. This finding offers potential therapeutic targets for lung cancer treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Lung adenocarcinoma (LUAD) metastasis is driven by an imbalance in tumor metastasis-promoting and suppressing genes.
  • The role of RNA-binding proteins (RBPs) in post-transcriptional regulation of metastasis-related genes in LUAD is not fully understood.

Purpose of the Study:

  • To investigate the roles of MCPIP3 and IGF2BP3 in LUAD metastasis.
  • To elucidate the post-transcriptional regulatory mechanisms involving MCPIP3, IGF2BP3, and METAP2 in LUAD.

Main Methods:

  • Bioinformatic analysis, qRT-PCR, immunohistochemistry, and immunoblotting to assess MCPIP3 and IGF2BP3 expression in LUAD tissues.
  • In vitro and in vivo experiments to evaluate the metastatic effects of MCPIP3 and IGF2BP3.
  • RNA sequencing, RNA pull-down, mass spectrometry, RIP, mRNA stability, and luciferase assays to determine the underlying molecular mechanisms.

Main Results:

  • MCPIP3 expression was low and IGF2BP3 expression was high in LUAD tissues, correlating with poor patient prognosis.
  • MCPIP3 inhibited, while IGF2BP3 promoted, LUAD cell metastasis in vitro and in vivo.
  • MCPIP3 degraded METAP2 mRNA, whereas IGF2BP3 stabilized METAP2 mRNA, with inverse correlations observed between MCPIP3/IGF2BP3 and METAP2 expression in LUAD tissues.

Conclusions:

  • MCPIP3 and IGF2BP3 antagonistically regulate LUAD cell metastasis by modulating METAP2 mRNA stability.
  • These findings highlight MCPIP3 and IGF2BP3 as potential therapeutic targets for controlling lung cancer metastasis.
Keywords:
IGF2BP3LUADMCPIP3METAP2metastasis

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