Functional analysis of microRNAs in human hepatocellular cancer stem cells.
Bottom Line: Importantly, inhibition of let-7 increases the chemosensitivity of HSCs to sorafenib and doxorubicin whereas silencing of miR-181 led to a reduction in HSCs motility and invasion.Knocking down IL-6 and Twist in HSCs significantly reduced let-7 and miR-181 expression and subsequently inhibited chemoresistance and cell invasion.In conclusion, alterations of IL-6- and Twist-regulated microRNA expression in HSCs play a part in tumour spreading and responsiveness to chemotherapy.
Affiliation: Department of Medicine and Scott & White Digestive Disease Research Center, Texas A&M Health Science Center College of Medicine and Scott & White Hospital, Temple, TX 76504, USA.Show MeSH
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Mentions: Human hepatocellular CSCs and parental HCC cells were provided by Celprogen Inc. (San Pedro, CA, USA). Three groups of HSCs were chosen for the studies from seven sets on the basis of self-renewal and real-time polymerase chain reaction (PCR) tests for the specific markers (Fig. 1). The selected group of cells was cultured in Human Liver Cancer Stem Cell Undifferentiated Media to keep the stem cell phenotype (HSC-SR), and in Human Liver Cancer Stem Cell Differentiated Media for 10 passages for differentiated progenitor cell phenotype (HSC-DF). Malignant HCC cells (HepG2) were obtained from the American Type Culture Collection (Manassas, VA, USA) and cultured as recommended by the supplier. Normal human liver stem cells were also obtained from Celprogen Inc.
Affiliation: Department of Medicine and Scott & White Digestive Disease Research Center, Texas A&M Health Science Center College of Medicine and Scott & White Hospital, Temple, TX 76504, USA.