Cancer stem cell–associated miRNAs serve as prognostic biomarkers in colorectal cancer

Shusuke Toden, Shigeyasu Kunitoshi, Jacob Cardenas, Jinghua Gu, Elizabeth Hutchins, Kendall Van Keuren-Jensen, Hiroyuki Uetake, Yuji Toiyama, Ajay Goel

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chemoresistance in cancer is linked to a subset of cancer cells termed “cancer stem cells” (CSCs), and in particular, those expressing the CD44 variant appear to represent a more aggressive disease phenotype. Herein, we demonstrate that CD44v6 represents a CSC population with increased resistance to chemotherapeutic agents, and its high expression is frequently associated with poor overall survival (OS) and disease-free survival (DFS) in patients with colorectal cancer (CRC). CD44v6+ cells showed elevated resistance to chemotherapeutic drugs and significantly high tumor initiation capacity. Inhibition of CD44v6 resulted in the attenuation of self-renewal capacity and resensitization to chemotherapeutic agents. Of note, miRNA profiling of CD44v6+ spheroid-derived CSCs identified a unique panel of miRNAs indicative of high self-renewal capacity. In particular, miR-1246 was overexpressed in CD44v6+ cells, and associated with poor OS and DFS in CRC patients. We demonstrate that CD44v6+ CSCs induced chemoresistance and enhance tumorigenicity in CRC cells, and this was in part orchestrated by a distinct panel of miRNAs with dysregulated profiles. These findings suggest that specific miRNAs could serve as therapeutic targets as well as promising prognostic biomarkers in patients with colorectal neoplasia.

Original languageEnglish
Article numbere125294
JournalJCI Insight
Volume4
Issue number6
DOIs
Publication statusPublished - Mar 21 2019

ASJC Scopus subject areas

  • Medicine(all)

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    Toden, S., Kunitoshi, S., Cardenas, J., Gu, J., Hutchins, E., Van Keuren-Jensen, K., Uetake, H., Toiyama, Y., & Goel, A. (2019). Cancer stem cell–associated miRNAs serve as prognostic biomarkers in colorectal cancer. JCI Insight, 4(6), [e125294]. https://doi.org/10.1172/jci.insight.125294