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DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective
Massimiliano Secchi1, Camilla Lodola1, Anna Garbelli1
1Institute of Molecular Genetics, IGM CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, 27100 Pavia, Italy.
Abstract:
RNA helicases of the DEAD-box family are involved in several metabolic pathways, from transcription and translation to cell proliferation, innate immunity and stress response. Given their multiple roles, it is not surprising that their deregulation or mutation is linked to different pathological conditions, including cancer. However, while in some cases the loss of function of a given DEAD-box helicase promotes tumor transformation, indicating an oncosuppressive role, in other contexts the overexpression of the same enzyme favors cancer progression, thus acting as a typical oncogene. The roles of two well-characterized members of this family, DDX3X and DDX5, as both oncogenes and oncosuppressors have been documented in several cancer types. Understanding the interplay of the different cellular contexts, as defined by the molecular interaction networks of DDX3X and DDX5 in different tumors, with the cancer-specific roles played by these proteins could help to explain their apparently conflicting roles as cancer drivers or suppressors.
Insights
DEAD-box RNA helicases have dual roles in cancer, acting as both oncogenes and oncosuppressors. Understanding their context-specific functions, like DDX3X and DDX5, is key to explaining their impact on tumor progression.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- DEAD-box RNA helicases are crucial for fundamental cellular processes including transcription, translation, and immune response.
- Dysregulation of these helicases is implicated in various pathologies, notably cancer.
- The roles of specific DEAD-box helicases, such as DDX3X and DDX5, can be context-dependent, acting as either oncogenes or oncosuppressors.
Purpose of the Study:
- To explore the dual oncogenic and oncosuppressive functions of DEAD-box RNA helicases, specifically DDX3X and DDX5.
- To investigate how cellular context and molecular interaction networks influence the roles of DDX3X and DDX5 in different cancer types.
- To elucidate the mechanisms behind the apparently contradictory roles of these helicases in cancer development and progression.
Main Methods:
- Review and analysis of existing literature on DEAD-box helicases (DDX3X, DDX5) in various cancer contexts.
- Examination of molecular interaction networks associated with DDX3X and DDX5 in different tumor types.
- Comparative analysis of studies reporting oncogenic versus oncosuppressive functions.
Main Results:
- DEAD-box helicases, including DDX3X and DDX5, exhibit context-dependent roles in cancer, functioning as either tumor promoters or suppressors.
- The specific molecular interactions and cellular environment significantly influence whether DDX3X or DDX5 acts as an oncogene or oncosuppressor.
- Evidence suggests that loss of function can promote tumors while overexpression can drive cancer progression for the same helicase.
Conclusions:
- The dual roles of DDX3X and DDX5 as oncogenes and oncosuppressors are explainable by their integration into distinct cellular contexts and molecular networks.
- Further research into these context-specific interactions is essential for a comprehensive understanding of their impact on cancer.
- Targeting DEAD-box helicases may require a nuanced approach, considering their specific roles in different tumor types.
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