RNF207 promotes colorectal cancer growth by regulating the Hippo-YAP pathway via enhanced MST1 ubiquitination and

Meng Wang1, Xing Wen1, Mei Yang2

  • 1Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Chengdu, 610031, China.

Abstract

Insights

Ring finger protein 207 (RNF207) promotes colorectal cancer growth by degrading MST1, leading to YAP pathway activation. Inhibiting RNF207 offers a potential therapeutic strategy for colorectal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Colorectal cancer (CRC) is a leading cause of cancer mortality with incompletely understood molecular drivers.
  • E3 ubiquitin ligases are emerging therapeutic targets in cancer due to their role in regulating oncoprotein stability.
  • Ring finger protein 207 (RNF207), an E3 ligase, has not been previously studied in the context of colorectal cancer.

Purpose of the Study:

  • To investigate the role and molecular mechanism of RNF207 in colorectal cancer progression.
  • To explore the potential of targeting RNF207 as a therapeutic strategy for colorectal cancer.

Main Methods:

  • Constructed RNF207 overexpression and knockdown colorectal cancer cell lines.
  • Assessed proliferation, migration, and invasion using CCK8, colony formation, and transwell assays.
  • Investigated RNF207's impact on the Hippo-YAP signaling pathway via Co-IP and ubiquitination assays.
  • Evaluated RNF207's effect on tumor growth in a nude mouse model.

Main Results:

  • Elevated RNF207 expression in colorectal tumors correlates with poor prognosis.
  • RNF207 enhances colorectal cancer cell proliferation and migration.
  • RNF207 promotes colorectal cancer progression by inducing MST1 degradation via K48 ubiquitination, leading to YAP pathway activation.
  • Reduced RNF207 expression inhibited colorectal cancer growth in vivo.

Conclusions:

  • RNF207 functions as an oncogene in colorectal cancer by degrading MST1 and activating the YAP pathway.
  • The RNF207-MST1-YAP axis represents a novel therapeutic target for colorectal cancer treatment.

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