CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression

Zhang, Huan; Yu, Haixin; Ren, Dianyuan; Sun, Yan; Guo, Feng; Cai, Hongkun; Zhou, Chen; Zhou, Yingke; Jin, Xin; Wu, Heshui

doi:10.7150/ijbs.68995

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Int J Biol Sci 2022; 18(8):3484-3497. doi:10.7150/ijbs.68995 This issue Cite

Research Paper

CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression

Huan Zhang^1,2,#, Haixin Yu^3,#, Dianyuan Ren^1,2, Yan Sun^1,2, Feng Guo^1,2, Hongkun Cai^1,2, Chen Zhou^1,2, Yingke Zhou^1,2, Xin Jin^4,5,✉, Heshui Wu^1,2,✉

1. Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
2. Sino-German Laboratory of Personalized Medicine for Pancreatic Cancer, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
3. Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
4. Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
5. Uro-Oncology Institute of Central South University, Changsha, Hunan, 410011, China
^#These authors contributed equally in this work

Citation:

Zhang H, Yu H, Ren D, Sun Y, Guo F, Cai H, Zhou C, Zhou Y, Jin X, Wu H. CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression. Int J Biol Sci 2022; 18(8):3484-3497. doi:10.7150/ijbs.68995. https://www.ijbs.com/v18p3484.htm

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Abstract

As a key reversible and heritable mechanism of transcriptional regulation, the epigenetic modification plays a crucial role in tumorigenesis. Of note, tobacco smoking induces epigenetic modifications to promote pancreatic cancer development. Chromobox protein homolog 3 (CBX3) acts as an epigenetic regulator, modulating gene expression of downstream targets via chromatin modifications. To date, the relationship between CBX3 and smoking in pancreatic cancer remains unknown. This study aimed to uncover the specific role and underlying mechanism of CBX3 in smoking-related pancreatic cancer. The bioinformatics analyses were conducted to identify CBX3 as a key player in tobacco-induced pancreatic cancer. The abnormal upregulation of CBX3 was associated with poor prognosis in pancreatic cancer patients. Moreover, cigarette smoke extract (CSE) exposure promoted the overexpression of Y-box-binding protein 1 (YBX1), which consequently led to upregulated CBX3 in pancreatic cancer cells. We also revealed that CBX3 enhanced pancreatic cancer progression, likely by inhibiting the expression of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) and promoting the activation of TGF‐β signaling. In summary, the YBX1/CBX3/SMURF2 signaling axis may be a promising therapeutic target in patients with smoking-related pancreatic cancer.

Keywords: CBX3, Smoking, Pancreatic cancer, YBX1, SMURF2

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APA

Zhang, H., Yu, H., Ren, D., Sun, Y., Guo, F., Cai, H., Zhou, C., Zhou, Y., Jin, X., Wu, H. (2022). CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression. International Journal of Biological Sciences, 18(8), 3484-3497. https://doi.org/10.7150/ijbs.68995.

ACS

Zhang, H.; Yu, H.; Ren, D.; Sun, Y.; Guo, F.; Cai, H.; Zhou, C.; Zhou, Y.; Jin, X.; Wu, H. CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression. Int. J. Biol. Sci. 2022, 18 (8), 3484-3497. DOI: 10.7150/ijbs.68995.

NLM

CSE

Zhang H, Yu H, Ren D, Sun Y, Guo F, Cai H, Zhou C, Zhou Y, Jin X, Wu H. 2022. CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression. Int J Biol Sci. 18(8):3484-3497.

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