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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
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Published on: October 30, 2013

MKRN2-Mediated Degradation of IGF2BP3 Suppresses MYC and Enhances CDK4/6 Inhibitor Sensitivity in Bladder Cancer

Qi Pan1, Qing Shi2,3, Yubo Zhao4

  • 1Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.

Cancers
|July 15, 2026
PubMed
Abstract

Insights

The MKRN2-IGF2BP3-MYC axis regulates CDK4/6 inhibitor sensitivity in bladder cancer. Targeting IGF2BP3 or boosting MKRN2 can overcome resistance and improve treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • CDK4/6 inhibitors are used for bladder cancer but resistance limits efficacy.
  • The role of the m6A reader IGF2BP3 in CDK4/6 inhibitor resistance is unknown.

Purpose of the Study:

  • Investigate the role of IGF2BP3 in bladder cancer's response to CDK4/6 inhibitors.
  • Elucidate the regulatory network involving IGF2BP3, MYC, and MKRN2.

Main Methods:

  • Transcriptomic profiling of palbociclib-treated bladder cancer cell lines.
  • Analysis of IGF2BP3 expression in The Cancer Genome Atlas (TCGA) and clinical cohorts.
  • Gain- and loss-of-function assays, RNA-binding, mRNA stability, ubiquitination, and in vivo studies.

Main Results:

  • IGF2BP3 was the sole differentially expressed m6A regulator post-palbociclib treatment.
  • Elevated IGF2BP3 correlated with poor prognosis and increased MYC/cell-cycle regulators, partially rescuing drug-induced arrest.
  • MKRN2 targeted IGF2BP3 for degradation, and its co-overexpression synergized with palbociclib to inhibit tumor growth.

Conclusions:

  • The MKRN2-IGF2BP3-MYC axis is crucial for CDK4/6 inhibitor sensitivity in bladder cancer.
  • Targeting IGF2BP3 or enhancing MKRN2 offers a potential strategy to overcome resistance to CDK4/6 inhibitors.
Keywords:
CDK4/6 inhibitionIGF2BP3MKRN2MYCbladder cancerproliferation

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