title: miR-888 is an expressed prostatic secretions-derived microRNA that promotes prostate cell growth and migration.
abstract: MicroRNAs (MiRNAs) are a growing class of small non-coding RNAs that exhibit widespread dysregulation in prostate cancer. We profiled miRNA expression in syngeneic human prostate cancer cell lines that differed in their metastatic potential in order to determine their role in aggressive prostate cancer. miR-888 was the most differentially expressed miRNA observed in human metastatic PC3-ML cells relative to non-invasive PC3-N cells, and its levels were higher in primary prostate tumors from cancer patients, particularly those with seminal vesicle invasion. We also examined a novel miRNA-based biomarker source called expressed prostatic secretions in urine (EPS urine) for miR-888 expression and found that its levels were preferentially elevated in prostate cancer patients with high-grade disease. These expression studies indicated a correlation for miR-888 in disease progression. We next tested how miR-888 regulated cancer-related pathways in vitro using human prostate cancer cell lines. Overexpression of miR-888 increased proliferation and migration, and conversely inhibition of miR-888 activity blocked these processes. miR-888 also increased colony formation in PC3-N and LNCaP cells, supporting an oncogenic role for this miRNA in the prostate. Our data indicates that miR-888 functions to promote prostate cancer progression and can suppress protein levels of the tumor suppressor genes RBL1 and SMAD4. This miRNA holds promise as a diagnostic tool using an innovative prostatic fluid source as well as a therapeutic target for aggressive prostate cancer.
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Lewis
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA; Department of Urology; Eastern Virginia Medical School and Urology of Virginia; Norfolk, VA USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lance
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Troyer
authors.affiliation: Graduate Program in Public Health; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Hind
authors.initials: H
authors.lastname: Beydoun
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hadley
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Orians
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Benzine
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Kenya
authors.initials: K
authors.lastname: Madric
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: O John
authors.initials: OJ
authors.lastname: Semmes
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Drake
authors.affiliation: Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
authors.forename: Aurora
authors.initials: A
authors.lastname: Esquela-Kerscher
mesh_terms: D014408:Biomarkers, Tumor / Q000652:urine*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism / Q000652:urine*; D060787:Neoplasm Grading; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C000589534:MIRN888 microRNA, human; D035683:MicroRNAs; D050720:Retinoblastoma-Like Protein p107; D051901:Smad4 Protein
keywords: EPS urine; expressed prostatic secretions urine; miR-888; miRNA; microRNA; non-coding RNA; prostate; prostate cancer