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Background <p>Colorectal cancer ranks second in global mortality rates, yet its molecular pathogenesis remains incompletely understood. Accumulating evidence indicates that E3 ubiquitin ligases modulate the activity and stability of critical oncoproteins via ubiquitination, positioning these enzymes as promising therapeutic targets for cancer intervention. The E3 ligase Ring finger protein 207 (RNF207), characterized as a regulator involved in heart disease, has not been investigated in colorectal cancer.</p> Methods <p>We constructed RNF207 overexpression and knockdown colorectal cancer cell lines, and investigated the effects of RNF207 on the proliferation and migration of colorectal cancer cells through experiments such as CCK8, colony formation, migration, and invasion assays. In colorectal cancer cell lines and human colorectal cancer tissues, the influence of RNF207 on the Hippo–YAP signaling pathway was extensively investigated. The mechanism by which RNF207 regulates P-YAP and MST1 was explored through Co-IP and ubiquitination experiments. Finally, the effect of RNF207 on the growth of colorectal cancer was investigated in nude mice.</p> Results <p>Here, we demonstrate that elevated RNF207 expression in colorectal tumors correlates with poor prognosis. Functional studies revealed that RNF207 enhances colorectal cancer cell proliferation, migration. Mechanistically, we identified that RNF207 promotes colorectal cancer progression through MST1-dependent regulation of Hippo–YAP signaling. Specifically, RNF207 interacts with MST1 and induces its proteasomal degradation via K48-linked ubiquitination dependent on the activity of E3 ligase, thereby attenuating YAP phosphorylation and activating YAP-driven transcription. Furthermore, the protein level of RNF207 was significantly negatively correlated with the protein levels of MST1 and P-YAP in colorectal tumors, and reducing the expression of RNF207 can effectively inhibit the growth of colorectal cancer.</p> Conclusions <p>Collectively, our findings uncover a novel oncogenic function of RNF207 in colorectal cancer, whereby it facilitates MST1 degradation through K48 ubiquitination, leading to YAP hyper-activation. Targeting RNF207–MST1–YAP axis may represent a potential therapeutic for colorectal cancer treatment.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月27日

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  • Meng Wang,
  • Xing Wen,
  • Mei Yang,
  • Jie Zhang,
  • Jianhui Gu,
  • Tianqi Lu

摘要

Background

Colorectal cancer ranks second in global mortality rates, yet its molecular pathogenesis remains incompletely understood. Accumulating evidence indicates that E3 ubiquitin ligases modulate the activity and stability of critical oncoproteins via ubiquitination, positioning these enzymes as promising therapeutic targets for cancer intervention. The E3 ligase Ring finger protein 207 (RNF207), characterized as a regulator involved in heart disease, has not been investigated in colorectal cancer.

Methods

We constructed RNF207 overexpression and knockdown colorectal cancer cell lines, and investigated the effects of RNF207 on the proliferation and migration of colorectal cancer cells through experiments such as CCK8, colony formation, migration, and invasion assays. In colorectal cancer cell lines and human colorectal cancer tissues, the influence of RNF207 on the Hippo–YAP signaling pathway was extensively investigated. The mechanism by which RNF207 regulates P-YAP and MST1 was explored through Co-IP and ubiquitination experiments. Finally, the effect of RNF207 on the growth of colorectal cancer was investigated in nude mice.

Results

Here, we demonstrate that elevated RNF207 expression in colorectal tumors correlates with poor prognosis. Functional studies revealed that RNF207 enhances colorectal cancer cell proliferation, migration. Mechanistically, we identified that RNF207 promotes colorectal cancer progression through MST1-dependent regulation of Hippo–YAP signaling. Specifically, RNF207 interacts with MST1 and induces its proteasomal degradation via K48-linked ubiquitination dependent on the activity of E3 ligase, thereby attenuating YAP phosphorylation and activating YAP-driven transcription. Furthermore, the protein level of RNF207 was significantly negatively correlated with the protein levels of MST1 and P-YAP in colorectal tumors, and reducing the expression of RNF207 can effectively inhibit the growth of colorectal cancer.

Conclusions

Collectively, our findings uncover a novel oncogenic function of RNF207 in colorectal cancer, whereby it facilitates MST1 degradation through K48 ubiquitination, leading to YAP hyper-activation. Targeting RNF207–MST1–YAP axis may represent a potential therapeutic for colorectal cancer treatment.