Membrane-associated RING-CH 7 inhibits stem-like capacities of bladder cancer cells by interacting with

Junlong Zhuang1,2,3, Lingli Zhang4,5,6, Siyuan Zhang7

  • 1Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

Cell & Bioscience
|March 11, 2024
PubMed
Abstract

Insights

Membrane-associated RING-CH 7 (MARCH7) inhibits bladder cancer stem-like cells by degrading NOD1. Targeting this MARCH7/NOD1 pathway offers a potential therapeutic strategy for bladder cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer stem-like cells (CSCs) are crucial for tumor progression and poor prognosis.
  • The molecular mechanisms governing CSC maintenance are not fully understood.
  • This study investigates the role of ubiquitin E3 ligase MARCH7 in bladder cancer CSCs.

Purpose of the Study:

  • To elucidate the function of MARCH7 in bladder cancer stem-like cells.
  • To determine the molecular mechanism by which MARCH7 influences CSCs.
  • To explore the therapeutic potential of targeting the MARCH7 pathway in bladder cancer.

Main Methods:

  • Utilized a bladder xenograft mouse model and analyzed MARCH7 expression via qPCR and IHC.
  • Assessed CSC-like properties (spheroid formation, proliferation, invasion) in bladder cancer cells with altered MARCH7 levels.
  • Investigated the MARCH7/NOD1 interaction and its downstream effects using co-immunoprecipitation, ubiquitination, and luciferase assays.

Main Results:

  • MARCH7 interacts with and targets NOD1 for ubiquitin-proteasome degradation.
  • NOD1 enhances CSC-like properties, including proliferation and invasion.
  • MARCH7 overexpression counteracted NOD1-mediated effects on bladder cancer CSCs in vitro and in vivo.

Conclusions:

  • MARCH7 acts as a tumor suppressor in bladder cancer by inhibiting CSCs.
  • This inhibition is mediated through MARCH7-induced degradation of NOD1.
  • The MARCH7/NOD1 pathway represents a potential therapeutic target for bladder cancer.

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