Characterization of SLC22A18 as a tumor suppressor and novel biomarker in colorectal cancer
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Yeonjoo Jung1,2,*, Yukyung Jun1,2,*, Hee-Young Lee1,2, Suyeon Kim1,2, Yeonhwa Jung1,2, Juhee Keum1,2, Yeo Song Lee3, Yong Beom Cho4, Sanghyuk Lee1,2 and Jaesang Kim1,2
1 Ewha Research Center for Systems Biology, Seoul, Korea
2 Department of Life Science, Ewha Womans University, Seoul, Korea
3 Samsung Biomedical Research Institute, Seoul, Korea
4 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
* Y. Jung and Y. Jun contributed equally to this work
Jaesang Kim, email:
Keywords: SLC22A18, tumor suppressor, colorectal cancer, G2/M arrest, KRAS
Received: November 26, 2014 Accepted: June 18, 2015 Published: June 28, 2015
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 KRASG12D-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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