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DEAD-Box Helicase 3 X-Linked Promotes Metastasis by Inducing Epithelial-Mesenchymal Transition via p62/Sequestosome-1

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Abstract

Background

DEAD-Box Helicase 3 X-Linked (DDX3X) is a member of the DEAD-box helicases that play a crucial role in RNA metabolism. Although DDX3X has been shown to contribute to tumorigenesis, the detailed mechanisms by which DDX3X functions in pancreatic ductal adenocarcinoma (PDAC) biogenesis remain poorly understood.

Aims

The goal of the present study was to elucidate the molecular mechanisms by which DDX3X contributes to tumorigenesis in PDAC.

Methods

Kaplan–Meier curves, the log-rank test, t test and Cox regression were used to analyze the relationship between DDX3X expression and the clinicopathological features of PDAC patients. DDX3X and p62 expression in human PDAC tissues was analyzed by immunohistochemistry. Monolayer scratch healing assays, cell migration assays and nude mouse lung metastasis models were used to evaluate the effect of DDX3X on metastasis in vitro and in vivo. Western blot analysis was used to assess the expression of proteins in the signaling pathway.

Results

We authenticated high DDX3X expression was associated with a poor prognosis in PDAC. The loss of DDX3X attenuated the migratory capacity of PDAC cells in vitro and in vivo. DDX3X was shown to facilitate epithelial-mesenchymal transition (EMT) and the phosphorylation of p65 and eIF2α. Moreover, DDX3X displayed oncogenic activity by promoting p62 accumulation.

Conclusions

Our results demonstrated that DDX3X activates NF-κB and promotes metastasis by inducing EMT via p62.

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Acknowledgments

All authors have read and approved the final manuscript. This research was supported by the Grants from Shaanxi Provincial Central Committee’s Special Fund Plan for Guiding Local Science and Technology Development, No. 2016ZY-HM-01.

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Authors and Affiliations

  1. Department of Digestive Disease and Gastrointestinal Motility Research Room, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xi Wu Road, Xi’an, 710004, Shaanxi Province, MI, China

    Ying Zheng, Suzhen Yang, Shuhui Wang, Lin Ma & Lei Dong

  2. State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, MI, China

    Bing Xu

  3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, MI, China

    Yitong Zhao

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  1. Ying Zheng
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  4. Suzhen Yang
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Correspondence to Lei Dong.

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Zheng, Y., Xu, B., Zhao, Y. et al. DEAD-Box Helicase 3 X-Linked Promotes Metastasis by Inducing Epithelial-Mesenchymal Transition via p62/Sequestosome-1. Dig Dis Sci 66, 3893–3902 (2021). https://doi.org/10.1007/s10620-020-06735-z

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  • DOI: https://doi.org/10.1007/s10620-020-06735-z

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