title: MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway.
abstract: Prostate cancer (PCa) is a leading cause of mortality and morbidity in men worldwide, and emerging evidence suggests that the CD44(high) prostate tumor-initiating cells (TICs) are associated with its poor prognosis. Although microRNAs are frequently dysregulated in human cancers, the influence of microRNAs on PCa malignancy and whether targeting TIC-associated microRNAs inhibit PCa progression remain unclear. In this study, we found that miR-320 is significantly downregulated in PCa. Overexpression of miR-320 in PCa cells decreases PCa tumorigenesis in vitro and in vivo. Global gene expression profiling of miR-320-overexpressing PCa cells reveals that downstream target genes of Wnt/β-catenin pathway and cancer stem cell markers are significantly decreased. MicroRNA-320 inhibits β-catenin expression by targeting the 3'-untranslated region of β-catenin mRNA. The reduction of miR-320 associated with increased β-catenin was also found in CD44(high) subpopulation of prostate cancer cells and clinical PCa specimens. Interestingly, knockdown of miR-320 significantly increases the cancer stem-like properties, such as tumorsphere formation, chemoresistance and tumorigenic abilities, although enriching the population of stem-like TICs among PCa cells. Furthermore, increased miR-320 expression in prostate stem-like TICs significantly suppresses stem cell-like properties of PCa cells. These results support that miR-320 is a key negative regulator in prostate TICs, and suggest developing miR-320 as a novel therapeutic agent may offer benefits for PCa treatment.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: I-Shan
authors.initials: IS
authors.lastname: Hsieh
authors.forename: Kung-Chao
authors.initials: KC
authors.lastname: Chang
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Tsai
authors.forename: Jhen-Yu
authors.initials: JY
authors.lastname: Ke
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.forename: Kuen-Haur
authors.initials: KH
authors.lastname: Lee
authors.forename: Shauh-Der
authors.initials: SD
authors.lastname: Yeh
authors.forename: Tse-Ming
authors.initials: TM
authors.lastname: Hong
authors.forename: Yuh-Ling
authors.initials: YL
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018874:Spheroids, Cellular / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; D049409:Luciferases, Firefly