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

// Yeonjoo Jung 1,2,* , Yukyung Jun 1,2,* , Hee-Young Lee 1,2 , Suyeon Kim 1,2 , Yeonhwa Jung 1,2 , Juhee Keum 1,2 , Yeo Song Lee 3 , Yong Beom Cho 4 , Sanghyuk Lee 1,2 and Jaesang Kim 1,2 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 Correspondence to: 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 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.