Wanted DEAD/H or Alive: Helicases Winding Up in Cancers

Abstract

Cancer is one of the most studied areas of human biology over the past century. Despite having attracted much attention, hype, and investments, the search to find a cure for cancer remains an uphill battle. Recent discoveries that challenged the central dogma of molecular biology not only further increase the complexity but also demonstrate how various types of noncoding RNAs such as microRNA and long noncoding RNA, as well as their related processes such as RNA editing, are important in regulating gene expression. Parallel to this aspect, an increasing number of reports have focused on a family of proteins known as DEAD/H-box helicases involved in RNA metabolism, regulation of long and short noncoding RNAs, and novel roles as "editing helicases" and their association with cancers. This review summarizes recent findings on the roles of RNA helicases in various cancers, which are broadly classified into adult solid tumors, childhood solid tumors, leukemia, and cancer stem cells. The potential small molecule inhibitors of helicases and their therapeutic value are also discussed. In addition, analyzing next-generation sequencing data obtained from public portals and reviewing existing literature, we provide new insights on the potential of DEAD/H-box helicases to act as pharmacological drug targets in cancers.

RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis

“…Therefore, we have numbered the uridine positions (1 through 6) arbitrarily starting from the first visible nucleotide in the RNA oligonucleotide. Several point mutations in DDX17 have been found in cancers, such as those in the large intestine, bladder, stomach, brain, and skin (Cai et al, 2017;Fuller-Pace, 2013b;Robert and Pelletier, 2013) ( Figure S2A). Some of the mutations involve residues that make direct contact with ATP, such as R432C in motif VI (colorectal carcinoma samples: COSMIC Project COSP44021; and skin cutaneous melanoma: TCGA; US; study ID: COSU540) and T143A in motif I (bladder cancer samples; study ID: COSU581) (Guo et al, 2013).…”

“…DDX17 has also been implicated in immunity by affecting viral infectivity (Lorgeoux et al, 2013;Moy et al, 2014;Sithole et al, 2018). Dysregulated expression of DDX17 has been associated with many cancers, including those in colon, prostate, breast, brain, lung, stomach, and blood (Cai et al, 2017;Fuller-Pace and Moore, 2011). While the long list of significant biological functions highlights the importance of DDX17, the multitasking nature of DDX17 has also made its mechanisms perplexing.…”

DDX3XRNAhelicase affects breast cancer cell cycle progression by regulating expression ofKLF4

“…Given the widespread activity of DEAD‐box helicases in regulating gene expression at different levels, and the numerous studies reporting their involvement in cellular growth , it is not surprising that alterations in their expression or function can potentially affect normal cellular homeostasis and contribute to cancer development and progression .…”

Diverse Roles of DEAD/DEAH-Box Helicases in Innate Immunity and Diseases

“…Although this makes the involvement of DEAD/DEAH-box helicases in cancer highly possible, the innate immunity-related roles of DEAD/DEAH-box helicases in cancer restriction and pathogenesis have not been investigated yet. However, a large number of DEAD/DEAH-box helicases have been implied in cancer [188,189].…”