title: miR-125b regulates side population in breast cancer and confers a chemoresistant phenotype.
abstract: Resistance to chemotherapy is a major obstacle for the effective treatment of breast cancer and is partially due to the presence of drug resistant stem cell-like side population (SP). Previous studies have shown elevated miR-125b is associated with chemoresistance and metastasis; however, the relationship between miR-125b and SP cells remains unknown. In this study, we isolated and characterized SP cells in a panel of breast cancer cell lines and primary cancer cells from breast cancer patients. SP cells showed cancer stem cells (CSCs) properties, including self-renewal, resistance to chemotherapy and high expression of stem cell markers. The percentage of SP cells was higher in chemotherapy resistant patients compared to that in chemotherapy responsive patients (5.8 ± 2.4% in non-responsive patients vs. 1.2 ± 0.5% in responsive patients, P = 0.012). Importantly, SP cells had higher level of miR-125b than NSP cells and the elevated miR-125b expression in chemoresistant cancer cells were due to high percentage of SP cells. Overexpression of miR-125b correlated with an increase in tumor SP and CSC property, whereas knockdown of miR-125b correlated with decreased incidence of SP. In addition, miR-125b overexpression in breast cancer cells induced epithelial-mesenchymal transition (EMT)-like cellular marker alteration, suggesting a potential mechanism of miR-125b in the regulation of cancer stem-like SP cells. Taken together, these results suggest an important role for miR-125b in breast cancer chemoresistance by maintaining cancer stem-like SP fraction, and raise the possibility that miR-125b may be a significant prognostic response marker for cancer therapy.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Hong-Jiang
authors.initials: HJ
authors.lastname: Wang
authors.forename: Ying-Qiu
authors.initials: YQ
authors.lastname: Guo
authors.forename: Guang
authors.initials: G
authors.lastname: Tan
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.forename: Ke-Jun
authors.initials: KJ
authors.lastname: Li
authors.forename: Zhong-Yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs
keywords: BREAST CANCER; CANCER STEM CELLS; CHEMORESISTANCE; SIDE POPULATION; miR-125B