RHOQ RNA editing in colorectal cancer. NGS in colorectal cancer

RNA editing can increase RNA sequence variation without alteration of DNA sequence. By comparing whole genome and transcriptome sequence data of a rectal cancer, we have found a novel tumor specific RNA editing in RHOQ. The A-to-I editing results in substitution of asparagine with serine at residue 136. We observed higher level of the RHOQ RNA editing in tumor compared with normal tissue in colorectal cancer. The degree of RNA editing was associated with RhoQ activity in colorectal cancer cell lines. RhoQ N136S amino acid substitution increased RhoQ activity, actin cytoskeletal reorganization, and invasion potential. KRAS mutation further increased the invasion potential of RhoQ N136S in vitro. Among colorectal cancer patients, recurrence was more frequently observed in patients with tumors having edited RHOQ and mutant KRAS. Collectively, we show that RNA editing is another mechanism of sequence alteration contributing to colorectal cancer progression.