RNA editing in RHOQ promotes invasion potential in colorectal cancer

Abstract

Novel A-to-I RNA editing in the coding sequence of RHOQ leads to an amino acid substitution that promotes invasion in colorectal cancer.

The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers

“…In prostate cancer, A-to-I RNA editing in the androgen receptor impairs the protein's ability to interact with androgenic or anti-androgenic ligands (Martinez et al, 2008); in liver cancer, the edited form of AZIN1 has a stronger affinity for antizyme and induces cytoplasmic-to-nuclear translocation of AZIN1 , and a low editing level is sufficient to confer more aggressive tumor behavior (Chen et al, 2013); in colorectal cancer, A-to-I RNA editing in RHOQ promotes the invasion potential (Han et al, 2014); and in gliboblastoma, ADAR2- mediated RNA editing in CDC14B modulates the Skp2/p21/p27 pathway and plays a critical role in the pathogenesis of this disease (Galeano et al, 2013). Despite these intriguing findings, the global pattern of A-to-I RNA editing in human cancer genomes have not been systematically characterized, and the functional importance and clinical relevance of RNA editing in cancer remain largely unknown.…”

A-to-I RNA Editing Contributes to Proteomic Diversity in Cancer

“…Although the vast majority of A-to-I editing events occur in non-coding regions, the absolute number of high-confidence missense RNA editing sites in humans is large (>1,000) (Bazak et al, 2014; Peng et al, 2012; Ramaswami et al, 2012; Ramaswami et al, 2013). Intriguingly, several individual editing events have been reported to play critical roles in tumorigenesis, such as AZIN1 editing in liver cancer (Chen et al, 2013), CDC14B editing in glioblastoma (Galeano et al, 2013), RHOQ editing in colorectal cancer (Han et al, 2014), SLC22A3 and IGFBP7 editing in esophageal cancer (Chen et al, 2017; Fu et al, 2017), PODXL editing in gastric cancer (Chan et al, 2016), and GABRA3 editing in breast cancer (Gumireddy et al, 2016). Using RNA-sequencing data from The Cancer Genome Atlas (TCGA), recent studies have detected a large number of A-to-I editing events in cancer transcriptomes, many of which show clinically relevant patterns (Fumagalli et al, 2015; Han et al, 2015; Paz-Yaacov et al, 2015).…”

RNA Editing Dynamically Rewrites the Cancer Code

“…For instance, in hepatocellular carcinoma, ADAR-mediated editing of AZIN1 (antizyme inhibitor 1) is increased, and this helps to drive the progression of disease through increased cell proliferation [9]. Similarly, in colorectal cancer, increased editing of RHOQ (Ras homolog family member Q) promotes invasion potential through deregulation of actin remodeling [10]. However, these studies do not fully address the role of ADAR in these cancers, because editing in both cases is much more widespread, potentially affecting thousands of sites within tens of transcripts.…”