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
Related in: MedlinePlus
Mentions: It has been suggested that tumour invasion and metastasis may be mediated by the CSC population [43, 44]. We observed human HCC cells and stem cells by light microscopy to examine invasion of the Matrigel. Movements of malignant cells in Matrigel were associated with formation of peripheral ruffles. Compared to HepG2 and N-LSC cells, HSCs had more cells with membrane ruffles, and cells were more invasive in the Matrigel (Fig. 7A and B). In vitro assays were used to compare sorted subpopulations from the perspective of differences in cell migration, and invasion (Fig. 7C and D). Oct-4+CD133+ cells were observed to be significantly more migratory towards serum (Fig. 6C), and significantly more invasive through ECM gel (Fig. 7D) than respective Oct-4−CD133− cell subsets (P < 0.001).
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.