miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells.
miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells.
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DOI：
10.1016/j.bbrc.2013.08.042
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发表时间：
2013-09-13
影响因子：
3.1
通讯作者：
Eibl, Guido
中科院分区：
文献类型：
--
作者：
Pham, Hung;Rodriguez, C. Ekaterina;Donald, Graham W.;Hertzer, Kathleen M.;Jung, Xiaoman S.;Chang, Hui-Hua;Moro, Aune;Reber, Howard A.;Hines, O. Joe;Eibl, Guido
小的非编码RNAs，microRNAs(MiRNA)，通过靶向3‘-非翻译区(3’-UTR)，抑制或加速消息RNA(MRNA)的翻译或降解，通过基因抑制来调节生长和生存。失控的miRNA表达有助于多种癌症的疾病进展，包括胰腺癌(PACA)。PACA组织和细胞表现出miRNA减少，环氧合酶(COX)-2升高和前列腺素E2(PGE2)增加，导致肿瘤生长和转移增加。以人PACA细胞株为研究对象，证明miRNA-143(miR-143)修复后可调节COX-2并抑制细胞增殖。MIR-143在ASPC-1、CAPAN-2和MIA-PACA-2中的表达水平分别为0.41±0.06、0.20±0.05和0.10±0.02。在BxPC-3、HPAF-II和PANC-1中未检测到MIR-143，这与丝裂原活化蛋白激酶(MAPK)和丝裂原活化蛋白激酶(MEK)的激活有关。经10μM的MEK抑制剂U0126和PD98059处理后，BxPC-3和HPAF-II的miR-143分别增加187±18和152±26倍，分别增加182±7和136±9倍。在60min时，MIR-143使BxPC-3和HPAF-II的COX-2mRNA稳定性分别降低了2.6±0.3倍和2.5±0.2倍。BxPC-3和HPAF-II中COX-2的表达和细胞增殖与miR-143的升高呈负相关。转染miR-143的BxPC-3和HPAF-II的PGE2水平分别下降39.3±5.0%和48.0±3.0%。修复miR-143可抑制COX-2、PGE2、细胞增殖和MEK/MAPK的激活，提示该途径参与了miR-143的表达调控。
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.
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