TRIM36 Inhibits the Development of AOM/DSS-Induced Colitis-Associated Colorectal Cancer by Promoting the Ubiquitination and Degradation of GRB7
Ju Wu
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorZhengbo Yang
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorXi Chen
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorShuangshuang Hou
Department of General Surgery, Fuyang Normal University Second Affiliated Hospital, Fuyang, China
Search for more papers by this authorNanbo Li
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
Search for more papers by this authorYaoyuan Chang
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorCorresponding Author
Jiajun Yin
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Correspondence: Jiajun Yin ([email protected])
Jian Xu ([email protected])
Search for more papers by this authorCorresponding Author
Jian Xu
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Correspondence: Jiajun Yin ([email protected])
Jian Xu ([email protected])
Search for more papers by this authorJu Wu
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorZhengbo Yang
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorXi Chen
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorShuangshuang Hou
Department of General Surgery, Fuyang Normal University Second Affiliated Hospital, Fuyang, China
Search for more papers by this authorNanbo Li
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
Search for more papers by this authorYaoyuan Chang
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Search for more papers by this authorCorresponding Author
Jiajun Yin
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Correspondence: Jiajun Yin ([email protected])
Jian Xu ([email protected])
Search for more papers by this authorCorresponding Author
Jian Xu
Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, China
Correspondence: Jiajun Yin ([email protected])
Jian Xu ([email protected])
Search for more papers by this authorJu Wu, Zhengbo Yang and Xi Chen contributed equally to this work and should be considered co-first author.
ABSTRACT
Colorectal cancer (CRC) is among the most common cancer types for both sexes. Tripartite motif 36 (TRIM36) has been reported to be aberrantly expressed in several cancer types, suggesting its involvement in cancer progression. However, the role of TRIM36 in the colorectal carcinogenesis remain unknown. In our in vivo experiments, we investigated the role of TRIM36 in AOM/DSS-induced colitis-associated carcinogenesis using TRIM36-knockout (TRIM36 KO) mice. Subsequently, we overexpressed and knocked down TRIM36 expression in two CRC cell lines to further confirm the role of TRIM36 in vitro. The UALCAN database revealed a significant decrease in TRIM36 levels in CRC tissues, including colon adenocarcinoma and rectum adenocarcinoma. A significant correlation was observed between TRIM36 levels and the histological subtype, individual cancer stage, and nodal metastasis status. The downregulation of TRIM36 in CRC tissues was further confirmed using our own collected clinical specimens. Low expression of TRIM36 was found to be associated with unfavorable overall survival and recurrence-free survival in CRC. TRIM36 KO promoted inflammation, inhibited autophagy, and facilitated the development of AOM/DSS-induced CRC. TRIM36 overexpression inhibited proliferation, migration, and invasion, while activated autophagy in CRC cells. TRIM36 directly bound to and regulated the ubiquitination of GRB7 protein. The tumor-suppressive role of TRIM36 in CRC cells was mediated by GRB7. The TRIM36/GRB7 axis may represent a promising therapeutic target for the treatment of CRC.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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