title: RNA editing in RHOQ promotes invasion potential in colorectal cancer.
abstract: RNA editing can increase RNA sequence variation without altering the DNA sequence. By comparing whole-genome and transcriptome sequence data of a rectal cancer, we found novel tumor-associated increase of RNA editing in ras homologue family member Q (RHOQ) transcripts. The adenosine-to-inosine (A-to-I) editing results in substitution of asparagine with serine at residue 136. We observed a higher level of the RHOQ RNA editing in tumor compared with normal tissue in colorectal cancer (CRC). The degree of RNA editing was associated with RhoQ protein activity in CRC 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 CRC patients, recurrence was more frequently observed in patients with tumors having edited RHOQ transcripts and mutations in the KRAS gene. In summary, we show that RNA editing is another mechanism of sequence alteration that contributes to CRC progression.
authors.affiliation: Department of Internal Medicine, 2 Department of Pathology, and 3 Department of Surgery, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.forename: Hwang-Phill
authors.initials: HP
authors.lastname: Kim
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Shin
authors.forename: Eun-Goo
authors.initials: EG
authors.lastname: Jeong
authors.forename: Won-Chul
authors.initials: WC
authors.lastname: Lee
authors.forename: Keon Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Sang Youn
authors.initials: SY
authors.lastname: Park
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Lee
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Won
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D000199:Actins; D012333:RNA, Messenger; D006160:Guanosine Triphosphate; C503256:RHOQ protein, human; D020741:rho GTP-Binding Proteins