title: MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells.
abstract: Inositol polyphosphate 4-phosphatase type II emerges as a tumor suppressor in prostate cancer, and its loss of expression is associated with poor prognosis for prostate cancer. However, the mechanism of downregulation of inositol polyphosphate 4-phosphatase type II in prostate cancer development has not yet been fully clarified. In this study, microRNA-590-3p was found to be upregulated in both prostate cancer tissues and cell lines. Overexpression of microRNA-590-3p by microRNA-590-3p mimics promoted prostate cancer cell proliferation and invasion and accelerated the growth of xenografted tumors, while microRNA-590-3p inhibitors contributed to inhibition of cellular proliferation and invasion as well as tumor growth. A dual-luciferase reporter assay and expression analysis further confirmed that inositol polyphosphate 4-phosphatase type II was a direct target of microRNA-590-3p. Enforced expression of microRNA-590-3p led to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines. Overexpression of inositol polyphosphate 4-phosphatase type II could reduce microRNA-590-3p-induced cell proliferation and invasion as well as tumor growth, and decrease microRNA-590-3p-mediated upregulation of cyclin D1 and downregulation of p21 expression in prostate cancer cells. Taken together, our findings reveal that microRNA-590-3p is a potential onco-microRNA that participates in carcinogenesis of human prostate cancer by suppressing inositol polyphosphate 4-phosphatase type II expression and involving the Akt/FoxO3a pathway. MicroRNA-590-3p may represent a potential therapeutic target for prostate cancer patients.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Haiwen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: C530104:CCND1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; C568221:MIRN590 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase
keywords: MicroRNA-590-3p; inositol polyphosphate 4-phosphatase type II; proliferation; prostate cancer