title: RKIP suppresses the proliferation and metastasis of breast cancer cell lines through up-regulation of miR-185 targeting HMGA2.
abstract: Raf-1 kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor in cancer cells. MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. In this study, we found the expression of RKIP and miR-185 in breast cancer tissues was significantly lower than that of in normal breast tissues. Over-expression of RKIP up-regulated miR-185 expression, inhibited breast cancer cell growth and invasion, and inhibited miR-185 target gene High-mobility group AT-hook 2 (HMGA2). HMGA2 is encoded by HMGA2 gene, which encodes a protein that belongs to the non-histone chromosomal high-mobility group (HMG) protein family. Moreover, RKIP knockdown attenuated the inhibition of breast cancer cell invasion and the expression of HMGA2 by miR-185. Forced HMGA2 overexpression could partly restore the inhibitory effect of miR-185 on breast cancer cell growth and invasion. Our findings newly described RKIP/miR-185 to HMGA2 link and provided a potential mechanism for breast cancer cell growth and invasion. It may illustrate the potential therapeutic utility of signaling pathway signatures.
authors.affiliation: Department of Breast and Thyroid, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Qiongyan
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Breast Surgery, The General Hospital of Beijing Military Region, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Fu
authors.affiliation: Department of Breast and Thyroid, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: wenjun_yi_xiangya@163.com.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Breast and Thyroid, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Pei
authors.affiliation: Department of Breast and Thyroid, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D025743:HMGA2 Protein; C552431:MIRN185 microRNA, human; D035683:MicroRNAs; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D012333:RNA, Messenger
keywords: Breast cancer; Growth; HMGA2; Invasion; MIR-185; RKIP