%0 Journal Article
%T A role for low-abundance miRNAs in colon cancer: the miR-206/Kr¨ąppel-like factor 4 (KLF4) axis
%A Mansi A Parasramka
%A W Dashwood
%A Rong Wang
%A Hassaan H Saeed
%A David E Williams
%A Emily Ho
%A Roderick H Dashwood
%J Clinical Epigenetics
%D 2012
%I BioMed Central
%R 10.1186/1868-7083-4-16
%X 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 Kr¨ąppel-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.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.MicroRNAs (miRNAs or miRs) influence multiple stages of cancer development, via post-transcriptional mechanisms that degrade or repress target messenger RNAs (mRNAs) [1]. Several miRNAs with critical roles in early embryonic development [2] become aberrantly expressed in tumors [3]. For example, miR-21 is a high-abundance miRNA upregulated in cancers of the breast, lung, colon, liver, pancreas, prostate, esophagus, brain, and thyroid; targets of miR-21 include phosphatase and tensin homolog, tropomyosin 1, and programmed cell death 4 [4,5].Evolutionarily conserved high-abundance miRNAs, such as miR-21, have been profiled in various human cancers [6-8], but little is known about the role of low-abundance miRNAs. We hypothesized that certain low-abundance miRNAs might regulate key players in normal physiology such that, under normal circumstances, their expres
%K Cancer stem cells
%K Colon cancer
%K Epigenetics
%K KLF4
%K microRNAs
%K miR-206
%K Pluripotency factors
%U http://www.clinicalepigeneticsjournal.com/content/4/1/16