title: miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells.
abstract: Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E2 (PGE2) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 μM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26-fold in BxPC-3 and 182 ± 7 and 136 ± 9-fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3-fold in BxPC-3 and 2.5 ± 0.2-fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE2 levels decreased by 39.3 ± 5.0% in BxPC-3 and 48.0 ± 3.0% in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE2, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.
authors: Department of Surgery, UCLA Center of Excellence in Pancreatic Diseases, UCLA David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, United States; Department of Medicine, Veterans Affair Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States.
authors: Hung
authors: H
authors: Pham
authors: C Ekaterina
authors: CE
authors: Rodriguez
authors: Graham W
authors: GW
authors: Donald
authors: Kathleen M
authors: KM
authors: Hertzer
authors: Xiaoman S
authors: XS
authors: Jung
authors: Hui-Hua
authors: HH
authors: Chang
authors: Aune
authors: A
authors: Moro
authors: Howard A
authors: HA
authors: Reber
authors: O Joe
authors: OJ
authors: Hines
authors: Guido
authors: G
authors: Eibl
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002070:Butadienes; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D009570:Nitriles; D012333:RNA, Messenger; C101743:RREB1 protein, human; D014157:Transcription Factors; C113580:U 0126; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; COX-2; CREB; Cyclooxygenase-2; MAPK; MAPK kinase; MEK; MTT; PGE(2); PKA; PaCa; Pancreatic cancer; Prostaglandin E(2); RREB1; cyclic AMP responsive element binding protein; cyclooxygenase-2; miR-143; microRNA-143; mitogen-activated protein kinase; pancreatic cancer; prostaglandin E(2); protein kinase A; ras responsive element binding protein
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