title: miR-9 Acts as an OncomiR in Prostate Cancer through Multiple Pathways That Drive Tumour Progression and Metastasis.
abstract: Identification of dysregulated microRNAs (miRNAs) in prostate cancer is critical not only for diagnosis, but also differentiation between the aggressive and indolent forms of the disease. miR-9 was identified as an oncomiR through both miRNA panel RT-qPCR as well as high-throughput sequencing analysis of the human P69 prostate cell line as compared to its highly tumorigenic and metastatic subline M12, and found to be consistently upregulated in other prostate cell lines including DU-145 and PC3. While miR-9 has been characterized as dysregulated either as an oncomiR or tumour suppressor in a variety of other cancers including breast, ovarian, and nasopharyngeal carcinomas, it has not been previously evaluated and proven as an oncomiR in prostate cancer. miR-9 was confirmed an oncomiR when found to be overexpressed in tumour tissue as compared to adjacent benign glandular epithelium through laser-capture microdissection of radical prostatectomy biopsies. Inhibition of miR-9 resulted in reduced migratory and invasive potential of the M12 cell line, and reduced tumour growth and metastases in male athymic nude mice. Analysis showed that miR-9 targets e-cadherin and suppressor of cytokine signalling 5 (SOCS5), but not NF-ĸB mRNA. Expression of these proteins was shown to be affected by modulation in expression of miR-9.
authors.affiliation: Department of Biochemistry & Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: S J
authors.identifier: http://orcid.org/0000-0003-0093-8261
authors.initials: SJ
authors.lastname: Seashols-Williams
authors.affiliation: Department of Bioinformatics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: W
authors.initials: W
authors.lastname: Budd
authors.affiliation: Department of Biochemistry & Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: G C
authors.initials: GC
authors.lastname: Clark
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Biochemistry & Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: R
authors.initials: R
authors.lastname: Daniel
authors.affiliation: Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: E
authors.initials: E
authors.lastname: Dragoescu
authors.affiliation: Department of Biochemistry & Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Z E
authors.initials: ZE
authors.lastname: Zehner
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009857:Oncogenes; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C408990:SOCS5 protein, human; D050826:Suppressor of Cytokine Signaling Proteins