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Characterization of SLC22A18 as a tumor suppressor and novel biomarker in colorectal cancer

Title
Characterization of SLC22A18 as a tumor suppressor and novel biomarker in colorectal cancer
Authors
Jung, YeonjooJun, YukyungLee, Hee-YoungKim, SuyeonJung, YeonhwaKeum, JuheeLee, Yeo SongCho, Yong BeomLee, SanghyukKim, Jaesang
Ewha Authors
이상혁김재상정연주
SCOPUS Author ID
이상혁scopus; 김재상scopus; 정연주scopus
Issue Date
2015
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
vol. 6, no. 28, pp. 25368 - 25380
Keywords
SLC22A18tumor suppressorcolorectal cancerG2/M arrestKRAS
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS scopus
Abstract
SLC22A18, solute carrier family 22, member 18, has been proposed to function as a tumor suppressor based on its chromosomal location at 11p15.5, mutations and aberrant splicing in several types of cancer and down-regulation in glioblastoma. In this study, we sought to demonstrate the significance of SLC22A18 as a tumor suppressor in colorectal cancer (CRC) and provide mechanistic bases for its function. We first showed that the expression of SLC22A18 is significantly down-regulated in tumor tissues using matched normal-tumor samples from CRC patients. This finding was also supported by publically accessible data from The Cancer Genome Atlas (TCGA). Functionally, SLC22A18 inhibits colony formation and induces of G2/M arrest consistent with being a tumor suppressor. Interestingly, suppression of KRAS by RNA interference promotes SLC22A18 expression, and expression of SLC22A18 in turn inhibits KRAS(G12D)-mediated anchorage independent growth of NIH3T3 cells indicating a mutual negative interaction. Finally, we evaluated diagnostic and prognostic values of SLC22A18 using clinical and gene expression data from TCGA which revealed a significantly worse long-term prognosis for patients with low level SLC22A18 expression. In sum, we established SLC22A18 as a tumor suppressor in colon epithelial cells and propose that SLC22A18 is potentially a marker of diagnostic and prognostic values.
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