DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway

Shen, Lin; Zhang, Jing; Xu, Meng; Zheng, Ying; Wang, Mo; Yang, Suzhen; Qin, Bin; Li, Shunle; Dong, Lei; Dai, Fei

doi:10.7150/ijbs.73491

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Theranostics

International Journal of Medical Sciences

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Journal of Cancer

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Int J Biol Sci 2022; 18(10):3918-3933. doi:10.7150/ijbs.73491 This issue Cite

Research Paper

DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway

Lin Shen^1*, Jing Zhang^2*, Meng Xu³, Ying Zheng¹, Mo Wang¹, Suzhen Yang¹, Bin Qin¹, Shunle Li³, Lei Dong^1✉, Fei Dai^1✉

1. Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
2. Department of Kidney Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
3. Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
*These authors contributed equally to this study.

Citation:

Shen L, Zhang J, Xu M, Zheng Y, Wang M, Yang S, Qin B, Li S, Dong L, Dai F. DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway. Int J Biol Sci 2022; 18(10):3918-3933. doi:10.7150/ijbs.73491. https://www.ijbs.com/v18p3918.htm

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Abstract

Objective: The treatment and prognosis of patients with advanced colorectal cancer (CRC) remain a difficult problem. Herein, we investigated the role of DEAD (Asp-Glu-Ala-Asp) box helicase 3 (DDX3) in CRC and proposed potential therapeutic targets for advanced CRC.

Methods: The expression of DDX3 in CRC and its effect on prognosis were explored by databases and CRC tissue microarrays. Stable DDX3 knockdown and overexpression cell lines were established with lentiviral vectors. The effects of DDX3 on CRC were investigated by functional experiments in vitro and in vivo. The molecular mechanism of DDX3 in CRC was explored by western blotting. Molecular-specific inhibitors were further used to explore potential therapeutic targets for advanced CRC.

Results: The expression of DDX3 was decreased in advanced CRC, and patients with low DDX3 expression had a poor prognosis. In vitro and in vivo experiments showed that low DDX3 expression promoted the proliferation, migration and invasion of CRC. DDX3 loss regulated E-cadherin and β-catenin signaling through the mitogen-activated protein kinase (MAPK) pathway as shown by western blotting. In addition, the MEK inhibitor, PD98059, significantly reduced the increased cell proliferation, migration and invasion caused by knockdown of DDX3.

Conclusions: DDX3 acts as a tumor suppressor gene in CRC. DDX3 loss in advanced cancer promotes cancer progression by regulating E-cadherin and β-catenin signaling through the MAPK pathway, and targeting the MAPK pathway may be a therapeutic approach for advanced CRC.

Keywords: DDX3, colorectal cancer, MAPK, E-cadherin, β-catenin

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APA

Shen, L., Zhang, J., Xu, M., Zheng, Y., Wang, M., Yang, S., Qin, B., Li, S., Dong, L., Dai, F. (2022). DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway. International Journal of Biological Sciences, 18(10), 3918-3933. https://doi.org/10.7150/ijbs.73491.

ACS

Shen, L.; Zhang, J.; Xu, M.; Zheng, Y.; Wang, M.; Yang, S.; Qin, B.; Li, S.; Dong, L.; Dai, F. DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway. Int. J. Biol. Sci. 2022, 18 (10), 3918-3933. DOI: 10.7150/ijbs.73491.

NLM

CSE

Shen L, Zhang J, Xu M, Zheng Y, Wang M, Yang S, Qin B, Li S, Dong L, Dai F. 2022. DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway. Int J Biol Sci. 18(10):3918-3933.

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