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

Yeonjoo Jung, Yukyung Jun, Hee Young Lee, Suyeon Kim, Yeonhwa Jung, Juhee Keum, Yeo Song Lee, Yong Beom Cho, Sanghyuk Lee, Jaesang Kim

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)25368-25380
Number of pages13
JournalOncotarget
Volume6
Issue number28
DOIs
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015.

Keywords

  • Colorectal cancer
  • G2/M arrest
  • KRAS
  • SLC22A18
  • Tumor suppressor

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