TitleA role for low-abundance miRNAs in colon cancer: the miR-206/Krüppel-like factor 4 (KLF4) axis.
Publication TypeJournal Article
Year of Publication2012
AuthorsParasramka MA, W Dashwood M, Wang R, Saeed HH, Williams DE, Ho E, Dashwood RH
JournalClin Epigenetics
Volume4
Issue1
Pagination16
Date Published2012 Sep 24
ISSN1868-7083
Abstract

UNLABELLED:

BACKGROUND: MicroRNAs (miRNAs or miRs) are short non-coding RNAs that affect the expression of genes involved in normal physiology, but that also become dysregulated in cancer development. In the latter context, studies to date have focused on high-abundance miRNAs and their targets. We hypothesized that among the pool of low-abundance miRNAs are some with the potential to impact crucial oncogenic signaling networks in colon cancer.

RESULTS: Unbiased screening of over 650 miRNAs identified miR-206, a low-abundance miRNA, as the most significantly altered miRNA in carcinogen-induced rat colon tumors. Computational modeling highlighted the stem-cell marker Krüppel-like factor 4 (KLF4) as a potential target of miR-206. In a panel of primary human colon cancers, target validation at the mRNA and protein level confirmed a significant inverse relationship between miR-206 and KLF4, which was further supported by miR-206 knockdown and ectopic upregulation in human colon cancer cells. Forced expression of miR-206 resulted in significantly increased cell proliferation kinetics, as revealed by real-time monitoring using HCT116 cells.

CONCLUSIONS: Evolutionarily conserved high-abundance miRNAs are becoming established as key players in the etiology of human cancers. However, low-abundance miRNAs, such as miR-206, are often among the most significantly upregulated miRNAs relative to their expression in normal non-transformed tissues. Low-abundance miRNAs are worthy of further investigation, because their targets include KLF4 and other pluripotency and cancer stem-cell factors.

DOI10.1186/1868-7083-4-16
Alternate JournalClin Epigenetics
PubMed ID23006636
PubMed Central IDPMC3506528
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States