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J Exp Med. 2014 Apr 7;211(4):613-21. doi: 10.1084/jem.20132209. Epub 2014 Mar 24.

RNA editing in RHOQ promotes invasion potential in colorectal cancer.

Author information

1
Department of Internal Medicine, 2 Department of Pathology, and 3 Department of Surgery, Seoul National University Hospital, Seoul 110-744, Korea.

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.

PMID:
24663214
PMCID:
PMC3978269
DOI:
10.1084/jem.20132209
[Indexed for MEDLINE]
Free PMC Article

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