TRIM28 protects CARM1 from proteasome-mediated degradation to prevent colorectal cancer metastasis

Jinyuan Cui; Jia Hu; Zhilan Ye; Yongli Fan; Yuqin Li; Guobin Wang; Lin Wang; Zheng Wang

doi:10.1016/j.scib.2019.05.024

TRIM28 protects CARM1 from proteasome-mediated degradation to prevent colorectal cancer metastasis

Sci Bull (Beijing). 2019 Jul 30;64(14):986-997. doi: 10.1016/j.scib.2019.05.024. Epub 2019 May 25.

Authors

Jinyuan Cui¹, Jia Hu², Zhilan Ye², Yongli Fan², Yuqin Li², Guobin Wang³, Lin Wang⁴, Zheng Wang⁵

Affiliations

¹ Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
² Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
³ Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: wgb@hust.edu.cn.
⁴ Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: lin_wang@hust.edu.cn.
⁵ Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: zhengwang@hust.edu.cn.

PMID: 36659810
DOI: 10.1016/j.scib.2019.05.024

Abstract

TRIM28 (Tripartite motif-containing protein 28), a member of TRIM family, is aberrantly expressed and reportedly has different functions in many types of human cancer. However, the biological roles of TRIM28 and related mechanism in colorectal cancer (CRC) remain unclear. Here, we showed that TRIM28 was downregulated in colorectal cancer compared with normal mucosa, especially at advanced stages, and acted as an independent prognostic factor of favorable outcome. Functional studies demonstrated that TRIM28 restrained CRC migration and invasion in vitro and in vivo. Mechanistically, we reported that CARM1 (co-activator-associated arginine methyltransferase1) was a critical player downstream of TRIM28. TRIM28 interacted with CARM1, and protected CARM1 from proteasome-mediated degradation through physical protein-protein interaction to suppress CRC metastasis. Further, TRIM28 suppressed the migration and invasion of CRC cells through inhibiting WNT/β-catenin signaling in a CARM1-dependent manner, but independent of CARM1's methyltransferase activity. The protein expression of CARM1 was positively correlated with TRIM28 in CRC tissues. Patients with high levels of TRIM28 and CARM1 had improved prognosis, whereas patients with low TRIM28 and CARM1 expression had the poor outcomes. Thus, our study reveals an inhibitory role of TRIM28 in CRC metastasis, which was achieved through a TRIM28-CARM1-WNT/β-catenin axis. This work provides potential prognostic and therapeutic targets for CRC treatment.

Keywords: CARM1; Colorectal cancer; Metastasis; TRIM28; Ubiquitination; WNT/β-catenin.