Int J Med Sci 2022; 19(3):596-608. doi:10.7150/ijms.67840 This issue Cite

Research Paper

Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity

Xinglin Li1,2*, Xiaoyun Chen1,3*, Jiebing Gao1,4, Jianzhong Xian1,5, Zhijun Li1, Lei Bi1, Min Yang1, Shuai Yang6, Hongjun Jin1✉, Hong Shan1,7✉

1. Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
2. Department of Ultrasound, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, Guangdong Province 518000, China
3. Department of Radiology, Zhongshan Affiliated Hospital, Guangzhou University of Chinese Medicine, Zhongshan, Guangdong Province 528400, China
4. Department of Radiology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
5. Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
6. Center of Oncology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
7. Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
* These authors contributed equally to this article.

Citation:
Li X, Chen X, Gao J, Xian J, Li Z, Bi L, Yang M, Yang S, Jin H, Shan H. Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity. Int J Med Sci 2022; 19(3):596-608. doi:10.7150/ijms.67840. https://www.medsci.org/v19p0596.htm
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Abstract

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Purpose: Mutations (K11E or E271K) of DEAD-box RNA helicase 24 (DDX24) were related to multi-organ venous lymphatic malformation syndrome (MOVLD). However, the relationship between these mutations and DDX24-function still remains unknown. Understanding whether K11E and E271K cause “loss-of-function” or “gain-of-function” for DDX24 is significant for related diseases. DDX24 was reported to be related to tumors closely, thus this study aims to explore how K11E and E271K affect DDX24-function in tumor proliferation.

Methods: Cell lines stably expressing wild-type DDX24, K11E-DDX24, E271K-DDX24, along with vector only based on Chinese hamster ovary cells (CHO) and Balb/c tumor-bearing mice models were constructed. Then immunofluorescence staining, proliferation assay and colony formation assay in vitro and 18F-FDG PET/CT-scan were performed. Finally, the tumor tissues were collected to perform transcriptome sequencing to predict the potential mechanism.

Results: Contrasted with CHO-WT-DDX24, CHO-K11E-DDX24 or CHO-E271K-DDX24 showed a decreased number of nucleoli, a slower proliferation rate and a lower colony formation rate significantly. Moreover, mice, inoculated with CHO-K11E-DDX24 or CHO-E271K-DDX24 cells, showed lower tumor formation rate, slower tumor growth rate, better prognosis, reduced standard uptake value and Ki of glucose in subcutaneous tumors. Sequencing indicated CHO-K11E-DDX24 or CHO-E271K-DDX24 caused increasing expression of TNF or chemokines and alteration in immune-related signal pathways.

Conclusion: K11E or E271K mutation could lead to “loss-of-function” of DDX24 in cell proliferation and tumor bearing mice, which may be acted by non-specific immune killing to inhibit tumor growth.

Keywords: Nucleolar, mutation, loss-of-function, DDX24


Citation styles

APA
Li, X., Chen, X., Gao, J., Xian, J., Li, Z., Bi, L., Yang, M., Yang, S., Jin, H., Shan, H. (2022). Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity. International Journal of Medical Sciences, 19(3), 596-608. https://doi.org/10.7150/ijms.67840.

ACS
Li, X.; Chen, X.; Gao, J.; Xian, J.; Li, Z.; Bi, L.; Yang, M.; Yang, S.; Jin, H.; Shan, H. Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity. Int. J. Med. Sci. 2022, 19 (3), 596-608. DOI: 10.7150/ijms.67840.

NLM
Li X, Chen X, Gao J, Xian J, Li Z, Bi L, Yang M, Yang S, Jin H, Shan H. Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity. Int J Med Sci 2022; 19(3):596-608. doi:10.7150/ijms.67840. https://www.medsci.org/v19p0596.htm

CSE
Li X, Chen X, Gao J, Xian J, Li Z, Bi L, Yang M, Yang S, Jin H, Shan H. 2022. Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity. Int J Med Sci. 19(3):596-608.

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