title: lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI.
abstract: Prostate cancer is a leading cause of cancer-related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Currently, limited knowledge is available concerning the role of long non-coding RNAs in prostate cancer metastasis. In this study, we found that long non-coding RNA H19 (H19) and H19-derived microRNA-675 (miR-675) were significantly downregulated in the metastatic prostate cancer cell line M12 compared with the non-metastatic prostate epithelial cell line P69. Upregulation of H19 in P69 and PC3 cells significantly increased the level of miR-675 and repressed cell migration; however, ectopic expression of H19 in M12 cells could not increase the level of miR-675 and therefore had no effect on cell migration. Furthermore, we found that the expression level of either H19 or miR-675 in P69 cells was negatively associated with the expression of transforming growth factor β induced protein (TGFBI), an extracellular matrix protein involved in cancer metastasis. Dual luciferase reporter assays showed that miR-675 directly bound with 3'UTR of TGFBI mRNA to repress its translation. Taken together, we show for the first time that the H19-miR-675 axis acts as a suppressor of prostate cancer metastasis, which may have possible diagnostic and therapeutic potential for advanced prostate cancer.
authors.affiliation: Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Miaojun
authors.initials: M
authors.lastname: Zhu
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.forename: Xian
authors.initials: X
authors.lastname: Zhao
authors.forename: Rong
authors.initials: R
authors.lastname: Deng
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Jianshe
authors.initials: J
authors.lastname: Yan
authors.forename: Jianxiu
authors.initials: J
authors.lastname: Yu
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D020413:3' Untranslated Regions; D016326:Extracellular Matrix Proteins; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C094335:H19 long non-coding RNA; C548379:MIRN675 microRNA, human
keywords: TGFBI; lncRNA H19; miR-675; prostate cancer; tumor metastasis