title: MicroRNA-9 is associated with epithelial-mesenchymal transition, breast cancer stem cell phenotype, and tumor progression in breast cancer.
abstract: MicroRNAs (miRNAs) are involved in the progression of breast cancer. Some miRNAs, especially the miR-200 family, miR-9, and miR-155 have been reported to be associated with epithelial-mesenchymal transition (EMT) and breast cancer stem cell (BCSC) phenotypes. This study was designed to evaluate the expression levels of these miRNAs in human breast cancer samples and analyzed their relationship with clinicopathologic features of the tumor including breast cancer subtype, EMT, BCSC phenotype, and prognosis. Expression levels of the miR-200 family, miR-9, and miR-155 were quantified using qRT-PCR. Breast cancer subtype, BCSC phenotype (CD44+/CD24- and ALDH1+), and expression of EMT markers (vimentin expression and E-cadherin loss) were evaluated by immunohistochemistry. miR-9 was more highly expressed in HER2+ and triple-negative subtypes than in luminal subtypes. Its expression level was significantly higher in tumors with high T stage, high histologic grade, p53 overexpression, and high proliferation index. Expression of miR-9 was also higher in tumors showing the CD44+/CD24- phenotype, vimentin expression, and E-cadherin loss. Furthermore, high level of miR-9 expression was found to be an independent prognostic factor for poor disease-free survival of the patients. Expression of miR-200a and miR-141 was highest in luminal A subtype, and miR-155 expression was highest in triple-negative subtype. Although the expression levels of some miR-200 family members and miR-155 showed difference with regard to EMT or BCSC phenotype, they were not associated with patients' prognosis. In conclusion, overexpression of miR-9 is found in tumors with aggressive phenotypes and is associated with poor prognosis in breast cancer, suggesting that it may serve as a potential biomarker for breast cancer progression and a target for treatment.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Moon
authors.initials: JM
authors.lastname: Gwak
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Kim
authors.forename: Yul Ri
authors.initials: YR
authors.lastname: Chung
authors.forename: Sumi
authors.initials: S
authors.lastname: Yun
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53