title: MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells.
abstract: MicroRNAs (miRNAs) are key regulators of tumor progression. Based on microarray data, we identified miR-99a as a potential tumor suppressor in breast cancer. Expression of miR-99a is frequently down-regulated in breast cancer tissues relative to normal breast tissues. Reduced miR-99a expression was highly associated with lymph node metastasis and shorter overall survival of patients with breast cancer. Gain- and loss-of-function studies revealed that, miR-99a significantly inhibits breast cancer cell proliferation, migration, and invasion. An integrated bioinformatics analysis identified HOXA1 mRNA as the direct functional target of miR-99a, and this regulation was confirmed by luciferase reporter assay. Furthermore, we showed for the first time that HOXA1 expression is elevated in breast cancer tissues. Knockdown of HOXA1 significantly inhibited breast cancer cell proliferation, migration and invasion, and restoration of HOXA1 partially rescued the inhibitory effect of miR-99a in breast cancer cells. Collectively, our data indicate that miR-99a plays a tumor-suppressor role in the development of breast cancer, and could serve as a potential therapeutic target for breast cancer treatment.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huo
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Cai
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Shangge
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China.|Department of Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000099261:Homeobox A1 Protein
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C561679:MIRN99 microRNA, human
keywords: HOXA1; breast cancer; invasion; miR-99a; proliferation