title: microRNA-335 inhibits proliferation, cell-cycle progression, colony formation, and invasion via targeting PAX6 in breast cancer cells.
abstract: microRNAs (miRNAs) have been demonstrated to play crucial roles in tumorigenesis. However, the molecular mechanism underlying the roles of miRNAs in breast cancer remains largely unknown. In this study, we showed that miR-335 is downregulated in a number of breast cancer tissues and cell lines. Luciferase reporter assays identified the paired box 6 gene (PAX6) as a novel target of miR-335. Further investigation revealed that miR-335 negatively regulates the expression of PAX6 in human breast cancer MCF-7 cells. Our results further suggested that overexpression of miR-335 inhibits MCF-7 cell proliferation by inducing cell-cycle arrest at the G1 phase via targeting PAX6. Western blot analysis showed that overexpression of miR-335 promotes p27 protein expression but inhibits cyclin D1 expression in MCF-7 cells; however, overexpression of PAX6 decreased the p27 protein level but increased the cyclin D1 protein level in MCF-7 cells. Furthermore, miR-335 overexpression reduced colony formation and cellular invasion in MCF-7 cells, an effect that was reversed by PAX6 overexpression. In conclusion, this study provides novel insights into the in vitro regulatory patterns of miRNA-335 and PAX6 in breast cancer, and indicates that miRNA-335 may constitute a promising candidate for the treatment of breast cancer.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yuanbiao
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Hepatobiliary and Endocrine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.
authors.forename: Quanqing
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Hepatobiliary and Endocrine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary and Endocrine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Pan
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics*; D014410:Tumor Stem Cell Assay
chemical_list: D020413:3' Untranslated Regions; D005136:Eye Proteins; D018398:Homeodomain Proteins; C556347:MIRN335 microRNA, human; D035683:MicroRNAs; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins