A role for low-abundance miRNAs in colon cancer: the miR-206/Krüppel-like factor 4 (KLF4) axis

Clinical Epigenetics

Roderick H Dashwood²  Emily Ho³  David E Williams¹  Hassaan H Saeed⁴  Rong Wang⁴  W Mohaiza Dashwood⁴  Mansi A Parasramka⁴ 

[1]Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA

[2]R.H. Dashwood, 479 Linus Pauling Science Center, Oregon State University, Corvallis, OR, 97331, USA

[3]School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA

[4]Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA

关键词: Pluripotency factors;    miR-206;    microRNAs;    KLF4;    Epigenetics;    Colon cancer;    Cancer stem cells;   

Others  :  791326
DOI  :  10.1186/1868-7083-4-16

 received in 2012-07-29, accepted in 2012-09-18,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Parasramka et al.; licensee BioMed Central Ltd.

【 图 表 】

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