Journal
CELL DEATH & DISEASE
Volume 12, Issue 4, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-021-03670-3
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Funding
- Natural Science Foundation Program of China Programs [81472740, 31701202, 81572866, 81773104]
- Frontier Exploration Program of Huazhong University of Science and Technology [2015TS153]
- Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College of HUST
- Academic Medical Doctor Supporting Program of Tongji Medical College of HUST
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TRIM39, upregulated in colorectal cancer tissues, plays a crucial role in promoting cancer progression by regulating autophagy pathway and p53 degradation, establishing a functional relationship between autophagy and CRC progression.
The biological function of TRIM39, a member of TRIM family, remains largely unexplored in cancer, especially in colorectal cancer (CRC). In this study, we show that TRIM39 is upregulated in tumor tissues compared to adjacent normal tissues and associated with poor prognosis in CRC. Functional studies demonstrate that TRIM39 deficiency restrains CRC progression in vitro and in vivo. Our results further find that TRIM39 is a positive regulator of autophagosome-lysosome fusion. Mechanistically, TRIM39 interacts with Rab7 and promotes its activity via inhibiting its ubiquitination at lysine 191 residue. Depletion of TRIM39 inhibits CRC progression and autophagic flux in a Rab7 activity-dependent manner. Moreover, TRIM39 deficiency suppresses CRC progression through inhibiting autophagic degradation of p53. Thus, our findings uncover the roles as well as the relevant mechanisms of TRIM39 in CRC and establish a functional relationship between autophagy and CRC progression, which may provide promising approaches for the treatment of CRC.
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