DEAD-box RNA helicases with special reference to p68: Unwinding their biology, versatility, and therapeutic opportunity in cancer.

ABSTRACT

In the era of advancement, the entire world continues to remain baffled by the increased rate of progression of cancer. There has been an unending search for novel therapeutic targets and prognostic markers to curb the oncogenic scenario. The DEAD-box RNA helicases are a large family of proteins characterized by their evolutionary conserved D-E-A-D (Asp-Glu-Ala-Asp) domain and merit consideration in the oncogenic platform. They perform multidimensional functions in RNA metabolism and also in the pathology of cancers. Their biological role ranges from ribosome biogenesis, RNA unwinding, splicing, modification of secondary and tertiary RNA structures to acting as transcriptional coactivators/repressors of various important oncogenic genes. They also play a crucial role in accelerating oncogenesis by promoting cell proliferation and metastasis. DDX5 (p68) is one of the archetypal members of this family of proteins and has gained a lot of attention due to its oncogenic attribute. It is found to be overexpressed in major cancer types such as colon, brain, breast, and prostate cancer. It exhibits its multifaceted nature by not only coactivating genes implicated in cancers but also mediating crosstalk across major signaling pathways in cancer. Therefore, in this review, we aim to illustrate a comprehensive overview of DEAD-box RNA helicases especially p68 by focusing on their multifaceted roles in different cancers and the various signaling pathways affected by them. Further, we have also briefly discoursed the therapeutic interventional approaches with the DEAD-box RNA helicases as the pharmacological targets for designing inhibitors to pave way for cancer therapy.