title: MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis.
abstract: MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Anping
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Cell Death and Cancer Genetics, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000401:mortality*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000401:mortality*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C486562:CAPRIN1 protein, human; D018797:Cell Cycle Proteins; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6
keywords: ccRCC; metastasis; miR-1; proliferation