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Long Noncoding RNA TUG1/miR-29c Axis Affects Cell Proliferation Invasion and Migration in Human Pancreatic Cancer

机译:长非编码RNA TUG1 / miR-29c轴影响人类胰腺癌中细胞的增殖侵袭和迁移。

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摘要

Given the low resection rate and chemoresistance of patients with pancreatic cancer (PC), their survival rates are typically poor. Long noncoding RNAs (lncRNAs) have recently been shown to play an important role in tumourigenesis and human cancer progression, including in PC. In this study, we aimed to investigate the role of taurine-upregulated gene 1 (TUG1) in PC. A quantitative polymerase chain reaction was used to analyse TUG1 expression in PC tissues and peritumoural normal tissues. TUG1 was overexpressed in PC tissues compared with that in peritumoural normal tissues, and the high expression of TUG1 was associated with the poor prognosis of patients with PC. Furthermore, TUG1 knockdown significantly inhibited the proliferation and invasion of PC cells both in vitro and in vivo, while overexpression TUG1 promoted tumour cell proliferation, migration, and invasion. TUG1 directly targeted miR-29c, a tumour suppressor in several cancers. TUG1 knockdown significantly increased the expression of miR-29c and subsequently induced the downregulation of integrin subunit beta 1 (ITGB1), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9). The downregulation of miR-29c abolished the TUG1 knockdown-mediated inhibition of tumour growth in vitro and in vivo, whereas the upregulation of miR-29c enhanced the effects of TUG1 knockdown on PC cells. In conclusion, we demonstrate for the first time the oncogenic role of TUG1 in PC. The downregulation of TUG1 significantly inhibited the growth and migratory ability of PC cells in vitro and in vivo by targeting miR-29c. Our study provides a novel potential diagnostic biomarker and therapeutic target for PC.
机译:鉴于胰腺癌(PC)患者的切除率和化学抗性较低,其生存率通常较差。长的非编码RNA(lncRNA)最近已显示在肿瘤发生和人类癌症进展中,包括在PC中起重要作用。在这项研究中,我们旨在调查牛磺酸上调基因1(TUG1)在PC中的作用。定量聚合酶链反应用于分析PC组织和肿瘤周围正常组织中TUG1的表达。与肿瘤周围正常组织相比,TUG1在PC组织中过表达,并且TUG1的高表达与PC患者的预后不良有关。此外,TUG1敲低显着抑制体外和体内PC细胞的增殖和侵袭,而过表达TUG1促进肿瘤细胞的增殖,迁移和侵袭。 TUG1直接靶向miR-29c,miR-29c是几种癌症中的一种肿瘤抑制因子。 TUG1敲低显着增加miR-29c的表达,并随后诱导整联蛋白亚基beta 1(ITGB1),基质金属蛋白酶2(MMP2)和基质金属蛋白酶9(MMP9)的下调。 miR-29c的下调消除了TUG1敲低介导的体内外肿瘤生长抑制作用,而miR-29c的上调增强了TUG1敲低对PC细胞的作用。总之,我们首次证明了TUG1在PC中的致癌作用。通过靶向miR-29c,TUG1的下调显着抑制了PC细胞在体外和体内的生长和迁移能力。我们的研究为PC提供了一种新型的潜在诊断生物标志物和治疗靶标。

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