Xintian Zhang, Han Yao, Yichao Hou, Kun Zhou, Yu Liang, Lidan Hou, Xingming Zhang, Wenfeng Wang, Leilei Du, Mengfei Yao, Jianhua Wang, Xiangjun Meng
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TRIM21 promotes colorectal cancer development through regulating DNA replication by TCF3/MCM2/5 axis.
Disrupting DNA replication has been employed for treating cancers. In the present study, we found that Tripartite motif containing 21 (TRIM21) was highly expressed in colorectal cancer (CRC) and could be valuable for predicting the prognosis of CRC patients. Further study demonstrated that TRIM21 positively regulated the expression of MCM2 and MCM5, DNA replication and proliferation of CRC cells both in vitro and in vivo. In addition, TRIM21 knockdown inhibited both replication initiation and velocity, and increased the chemosensitivity of CRC cells to 5-FU and SN-38. Our study also revealed that DNA replication inhibition following TRIM21 knockdown could not be restored by cell cycle checkpoint kinase inhibitors, but partially by Transcription Factor 3 (TCF3) knockdown. TCF3 directly suppressed MCM2 and MCM5 transcription, inhibiting DNA replication. In summary, TRIM21 could influence tumor development and chemosensitivity to replication inhibitors by regulating DNA replication through the TCF3/MCM2/5 axis, suggesting a promising potential for CRC in the clinic.
期刊介绍：
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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