Chuan-Chuan Chao1, Daphne Kan2, Kuo-Shyan Lu1, Chung-Liang Chien3. 1. Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan. 2. Center of Genomic Medicine, National Taiwan University, 6F., No. 2, Syu-Jhou Road, Taipei 100, Taiwan. 3. Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Center of Genomic Medicine, National Taiwan University, 6F., No. 2, Syu-Jhou Road, Taipei 100, Taiwan. Electronic address: chien@ntu.edu.tw.
Abstract
BACKGROUND: Sphere formation, one method for identifying self-renewal ability, has been used to report that cancer stem-like cells exist in rat C6 glioma cells. Recent studies suggested that cancer stem-like cells share the stem cell properties of self-renewal and multipotent ability of neural stem cells and might be regulated by microRNAs (miRNAs). However, the mechanism of miRNA involvement in the sphere formation and neural differentiation abilities of cancer stem-like cells is poorly understood. RESULTS: We found that miRNA-30c could assist in sphere formation of C6 cells under defined conditions in neural stem cell medium DMEM/F12-bFGF-EGF-B27. Moreover, overexpression of miRNA-30c might reduce 3-isobutyl-1-methylxanthine (IBMX)-induced neural differentiation, as the expression of neural markers, especially glial fibrillary acidic protein (GFAP), decreased. Further experiments revealed that miRNA-30c inhibited the IBMX-induced astrocyte differentiation via targeting the upstream genes and inactivating phosphorylation of STAT3 of the JAK-STAT3 pathway. Subsequently, the expression of GFAP was reduced and the number of astrocyte differentiation from C6 cells decreased. CONCLUSIONS: Our findings suggest that miRNA-30c could play a regulatory role in self-renewal and neural differentiation in C6 glioma cells.
BACKGROUND: Sphere formation, one method for identifying self-renewal ability, has been used to report that cancer stem-like cells exist in ratC6 glioma cells. Recent studies suggested that cancer stem-like cells share the stem cell properties of self-renewal and multipotent ability of neural stem cells and might be regulated by microRNAs (miRNAs). However, the mechanism of miRNA involvement in the sphere formation and neural differentiation abilities of cancer stem-like cells is poorly understood. RESULTS: We found that miRNA-30c could assist in sphere formation of C6 cells under defined conditions in neural stem cell medium DMEM/F12-bFGF-EGF-B27. Moreover, overexpression of miRNA-30c might reduce 3-isobutyl-1-methylxanthine (IBMX)-induced neural differentiation, as the expression of neural markers, especially glial fibrillary acidic protein (GFAP), decreased. Further experiments revealed that miRNA-30c inhibited the IBMX-induced astrocyte differentiation via targeting the upstream genes and inactivating phosphorylation of STAT3 of the JAK-STAT3 pathway. Subsequently, the expression of GFAP was reduced and the number of astrocyte differentiation from C6 cells decreased. CONCLUSIONS: Our findings suggest that miRNA-30c could play a regulatory role in self-renewal and neural differentiation in C6 glioma cells.