Deltex E3 ubiquitin ligase 3 inhibits colorectal cancer cell growth and regulates cell cycle progression via upregulating E2F transcription factor 1

被引:6
作者
Xu, Hongli [1 ,2 ,3 ]
Liang, Shengnan [1 ]
Hu, Junjie [2 ,3 ]
Liu, Wentong [1 ]
Dong, Zhiqiang [1 ,2 ,4 ]
Wei, Shaozhong [1 ,2 ,3 ]
机构
[1] Huazhong Agr Univ, Coll Biomed & Hlth, Coll Life Sci & Technol, Wuhan, Peoples R China
[2] Huazhong Univ Sci & Technol, Hubei Canc Hosp, Tongji Med Coll, Wuhan, Peoples R China
[3] Colorectal Canc Med Res Ctr Hubei, Wuhan, Peoples R China
[4] Taihe Hosp, Brain Res Inst, Shiyan, Peoples R China
关键词
Cell cycle progression; Colorectal cancer; Cyclin D3; Deltex E3 ubiquitin ligase 3; E2F transcription factor 1; GENE-EXPRESSION; PROLIFERATION; PROMOTE;
D O I
10.1007/s11033-021-06916-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background The mortality rate of colorectal cancer (CRC) remains high in developing countries. Interventions that can inhibit the proliferation of tumor cells represent promising strategies in CRC treatment. Deltex E3 ubiquitin ligase 3 (DTX3) plays an essential role in tumor development and may predict the outcome of cancer patients. This study aimed to investigate the regulatory mechanisms of DTX3 in CRC progression. Methods and results The expression of DTX3 was significantly downregulated in CRC tissues relative to normal colorectal tissues. DTX3 overexpression inhibited, while DTX3 knockout promoted the colony-forming capacity and proliferation of CRC cells. E2F transcription factor 1 (E2F1) is a key mediator of cell cycle progression that participates in the progression, metastasis, and chemoresistance of CRC. Further analysis revealed that DTX3 regulated the transcriptional activity of E2F1 in CRC cells. The transcription by E2F1 was significantly reduced with the increase in the cellular level of DTX3, while DTX3 knockout exerted an opposite effect. DTX3 knockout also increased the expression of E2F1 target genes involved in cell cycle progression, CDC2 and Cyclin D3, while PD 0332991, an inhibitor of E2F1 transcription, inhibited the expression of both proteins. Conclusions In conclusion, DTX3 regulated CRC cell growth via regulating E2F1 and its downstream genes. These findings support further exploration of DTX3 as a potential therapeutic target for CRC.
引用
收藏
页码:1661 / 1668
页数:8
相关论文
共 29 条
  • [1] Global trends in colorectal cancer mortality: projections to the year 2035
    Araghi, Marzieh
    Soerjomataram, Isabelle
    Jenkins, Mark
    Brierley, James
    Morris, Eva
    Bray, Freddie
    Arnold, Melina
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2019, 144 (12) : 2992 - 3000
  • [2] Perspective on the dynamics of cancer
    Derbal, Youcef
    [J]. THEORETICAL BIOLOGY AND MEDICAL MODELLING, 2017, 14
  • [3] Ubiquitination of NOTCH2 by DTX3 suppresses the proliferation and migration of human esophageal carcinoma
    Ding, Xin-Yu
    Hu, Hai-Yang
    Huang, Ke-Nan
    Wei, Rong-Qiang
    Min, Jie
    Qi, Chen
    Tang, Hua
    Qin, Xiong
    [J]. CANCER SCIENCE, 2020, 111 (02) : 489 - 501
  • [4] Prognostic role of cyclin D2/D3 in multiple human malignant neoplasms: A systematic review and meta-analysis
    Ding, Zuo-you
    Li, Ran
    Zhang, Qi-jie
    Wang, Yi
    Jiang, Yi
    Meng, Qing-yang
    Xi, Qiu-lei
    Wu, Guo-hao
    [J]. CANCER MEDICINE, 2019, 8 (06): : 2717 - 2729
  • [5] Regulation of E2F1 Transcription Factor by Ubiquitin Conjugation
    Dubrez, Laurence
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (10)
  • [6] Signaling Pathways that Control Cell Proliferation
    Duronio, Robert J.
    Xiong, Yue
    [J]. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2013, 5 (03):
  • [7] Fang ZJ, 2020, AM J CANCER RES, V10, P757
  • [8] E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2
    Fang, Zejun
    Gong, Chaoju
    Liu, Hong
    Zhang, Xiaomin
    Mei, Lingming
    Song, Mintao
    Qiu, Lanlan
    Luo, Shuchai
    Zhu, Zhihua
    Zhang, Ronghui
    Gu, Hongqian
    Chen, Xiang
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2015, 464 (02) : 407 - 415
  • [9] An integrated genomics approach identifies drivers of proliferation in luminal-subtype human breast cancer
    Gatza, Michael L.
    Silva, Grace O.
    Parker, Joel S.
    Fan, Cheng
    Perou, Charles M.
    [J]. NATURE GENETICS, 2014, 46 (10) : 1051 - 1059
  • [10] Phosphorylation of MAVS/VISA by Nemo-like kinase (NLK) for degradation regulates the antiviral innate immune response
    Li, Shang-Ze
    Shu, Qi-Peng
    Song, Yang
    Zhang, Hui-Hui
    Liu, Yi
    Jin, Bing-Xue
    Liuyu, Tian-Zi
    Li, Chao
    Huang, Xi-Chen
    Du, Run-Lei
    Song, Wei
    Zhong, Bo
    Zhang, Xiao-Dong
    [J]. NATURE COMMUNICATIONS, 2019, 10 (1)