Related Experiment Video
Updated: Sep 28, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24
Xinglin Li1,2, Xiaoyun Chen1,3, Jiebing Gao1,4
1Guangdong 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.
Abstract:
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.
Insights
Mutations K11E and E271K in DEAD-box RNA helicase 24 (DDX24) cause a loss-of-function, inhibiting tumor cell proliferation and growth. This suggests DDX24 mutations may be targeted for cancer therapy by enhancing immune responses.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Mutations in DEAD-box RNA helicase 24 (DDX24) are linked to multi-organ venous lymphatic malformation syndrome (MOVLD).
- The functional impact of specific DDX24 mutations (K11E, E271K) on cellular processes, particularly tumor proliferation, remains unclear.
- Understanding these mutations' effects is crucial for developing therapeutic strategies for DDX24-associated diseases, including cancers.
Purpose of the Study:
- To investigate the functional consequences of K11E and E271K mutations in DDX24.
- To determine if these mutations result in a loss-of-function or gain-of-function relevant to tumor proliferation.
- To explore the potential mechanisms by which these mutations affect tumor growth and development.
Main Methods:
- Established Chinese hamster ovary (CHO) cell lines stably expressing wild-type DDX24, K11E-DDX24, and E271K-DDX24.
- Utilized Balb/c mice models for in vivo tumor formation and growth studies.
- Performed immunofluorescence staining, in vitro proliferation and colony formation assays, 18F-FDG PET/CT scans, and transcriptome sequencing.
Main Results:
- CHO cells expressing K11E-DDX24 or E271K-DDX24 exhibited significantly decreased nucleoli counts, proliferation rates, and colony formation.
- Mice inoculated with mutant DDX24-expressing cells showed reduced tumor formation, slower growth, and improved prognosis.
- Transcriptome analysis revealed altered expression of TNF and chemokines, indicating modulation of immune-related signaling pathways.
Conclusions:
- The K11E and E271K mutations confer a loss-of-function to DDX24 concerning cell proliferation and tumor development.
- The observed inhibition of tumor growth may involve enhanced non-specific immune responses against tumor cells.
- These findings highlight the potential of targeting DDX24 function in cancer therapy.
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:38The Ras Gene
Ras is a...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...