CBX2 Deletion Suppresses Growth and Metastasis of Colorectal Cancer by Mettl3-p38/ERK MAPK Signalling Pathway

被引:9
作者
Sun, Rui [1 ]
Tu, Xucan [1 ]
Chan, Shixin [1 ]
Wang, Xu [1 ]
Ji, Yizhong [1 ]
Wang, Zhenglin [1 ]
Yu, Zhen [1 ]
Zuo, Xiaomin [1 ]
Zhang, Qing [2 ]
Chen, Jiajie [4 ]
Han, Qijun [1 ]
Wang, Ming [1 ]
Zhao, Hu [1 ]
Zhang, Huabing [2 ,3 ]
Chen, Wei [1 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Gen Surg, Hefei 230032, Anhui, Peoples R China
[2] Anhui Med Univ, Metab Dis Res Ctr, Sch Basic Med, Dept Biochem & Mol Biol, Hefei 230032, Peoples R China
[3] Anhui Prov Inst Translat Med, Hefei 230032, Peoples R China
[4] Anhui Med Univ, Affiliated Hosp 1, Dept Dermatol, Hefei 230032, Peoples R China
基金
中国国家自然科学基金;
关键词
CBX2; METTL3; MAPK signal pathway; proliferation; metastasis; liver metastasis; METTL3; PROLIFERATION; KINASE; APOPTOSIS; MIGRATION; PROTEINS; FAMILY;
D O I
10.7150/jca.92633
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Colorectal cancer (CRC) seriously endangers human health owing to its high morbidity and mortality. Previous studies have suggested that high expression of CBX2 may be associated with poor prognosis in CRC patients. However, its functional role in CRC remains to be elucidated. Herein, we found that CBX2 overexpression in colorectal cancer tissue compared with adjacent tissues. Additionally, forest maps and the nomogram model indicated that elevated CBX2 expression was an independent prognostic factor in CRC. Moreover, we confirmed that the deletion of CBX2 markedly suppressed the proliferation and migration of CRC cells in vitro and in vivo. Furthermore, downregulation of CBX2 promotes CRC cell apoptosis and hinders the cell cycle. Mechanistically, our data demonstrated that deletion of CBX2 inhibited the MAPK signaling pathway by regulating the protein levels of Mettl3. In conclusion, our study demonstrated that CBX2 is a vital tumor suppressor in CRC and could be a promising anti-cancer therapeutic target.
引用
收藏
页码:2123 / 2136
页数:14
相关论文
共 41 条
[31]   Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J].
Sung, Hyuna ;
Ferlay, Jacques ;
Siegel, Rebecca L. ;
Laversanne, Mathieu ;
Soerjomataram, Isabelle ;
Jemal, Ahmedin ;
Bray, Freddie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2021, 71 (03) :209-249
[32]   IHC Profiler: An Open Source Plugin for the Quantitative Evaluation and Automated Scoring of Immunohistochemistry Images of Human Tissue Samples [J].
Varghese, Frency ;
Bukhari, Amirali B. ;
Malhotra, Renu ;
De, Abhijit .
PLOS ONE, 2014, 9 (05)
[33]   Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation [J].
Wang, Huamin ;
Hu, Xiang ;
Huang, Mingyan ;
Liu, Juan ;
Gu, Yan ;
Ma, Lijia ;
Zhou, Qi ;
Cao, Xuetao .
NATURE COMMUNICATIONS, 2019, 10 (1)
[34]   Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis [J].
Wang, Hui ;
Tian, Tian ;
Zhang, Jinhua .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (16)
[35]   Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis [J].
Wei, Chen ;
Yang, Chaogang ;
Wang, Shuyi ;
Shi, Dongdong ;
Zhang, Chunxiao ;
Lin, Xiaobin ;
Liu, Qing ;
Dou, Rongzhang ;
Xiong, Bin .
MOLECULAR CANCER, 2019, 18 (1)
[36]   CBX2 identified as driver of anoikis escape and dissemination in high grade serous ovarian cancer [J].
Wheeler, Lindsay J. ;
Watson, Zachary L. ;
Qamar, Lubna ;
Yamamoto, Tomomi M. ;
Post, Miriam D. ;
Berning, Amber A. ;
Spillman, Monique A. ;
Behbakht, Kian ;
Bitler, Benjamin G. .
ONCOGENESIS, 2018, 7
[37]   Silencing of MBD2 and EZH2 inhibits the proliferation of colorectal carcinoma cells by rescuing the expression of SFRP [J].
Xie, Yang ;
Wang, Feng ;
Yu, Jun ;
Zhang, Jing ;
Liu, Yuting ;
Li, Mengying ;
Qi, Jian .
ONCOLOGY REPORTS, 2021, 46 (06)
[38]   CBX2 depletion inhibits the proliferation, invasion and migration of gastric cancer cells by inactivating the YAP/β-catenin pathway [J].
Zeng, Miaomiao ;
Li, Bangxue ;
Yang, Lei ;
Guan, Quanlin .
MOLECULAR MEDICINE REPORTS, 2021, 23 (02)
[39]   Interaction with tumor-associated macrophages promotes PRL-3-induced invasion of colorectal cancer cells via MAPK pathway-induced EMT and NF-κB signaling-induced angiogenesis [J].
Zhang, Tao ;
Liu, Lu ;
Lai, Wei ;
Zeng, Yujie ;
Xu, Heyang ;
Lan, Qiusheng ;
Su, Pengwei ;
Chu, Zhonghua .
ONCOLOGY REPORTS, 2019, 41 (05) :2790-2802
[40]   Expression and prognostic significance of CBX2 in colorectal cancer: database mining for CBX family members in malignancies and vitro analyses [J].
Zhou, He ;
Xiong, Yong ;
Liu, Zuoliang ;
Hou, Songlin ;
Zhou, Tong ;
Xiong, Yongfu .
CANCER CELL INTERNATIONAL, 2021, 21 (01)