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长链非编码RNA lnc-PCTST通过下调TACC-3抑制胰腺癌进展来预测预后。

Long non-coding RNA lnc-PCTST predicts prognosis through inhibiting progression of pancreatic cancer by downregulation of TACC-3.

作者信息

Wang Yandong, Ding Xiangya, Hu Hao, He Yuan, Lu Zipeng, Wu Pengfei, Tian Lei, Xia Tianfang, Yin Jie, Yuan Hao, Shi Guodong, Liu Dongfang, Jiang Kuirong, Miao Yi

机构信息

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of General surgery, The Second People's Hospital of Wuhu, Wuhu, China.

出版信息

Int J Cancer. 2018 Dec 15;143(12):3143-3154. doi: 10.1002/ijc.31657. Epub 2018 Nov 15.

Abstract

Pancreatic cancer (PC), which is one of the most lethal of malignancies and a major health burden, is associated with a dismal prognosis despite current therapeutic advances. Numerous long noncoding RNAs (lncRNA) have shown to be essential for PC tumorigenesis and progression. Nevertheless, the exact expression pattern of lnc-PCTST and its clinical significance still remain unclear. This study investigates the expression pattern of lnc-PCTST and its associated mRNA in three paired PC tissues and adjacent non-tumor tissues by Microarray-coarray approach. Briefly, our data demonstrated that lnc-PCTST expression is down-regulated in PC tissues. Also, lnc-PCTST has shown to be negatively correlated with transforming acidic coiled-coil 3 (TACC-3) expression. This expression pattern was further confirmed following qRT-PCR validation of 34 out of 48 paired cancer tissues. Furthermore, lnc-PCTST overexpression in PC cell lines inhibited cell proliferation and invasion in vitro, and tumorigenesis in vivo (using nude mice as animal model), but did not altered cell migration. Moreover, lnc-PCTST overexpression increased E-cadherin and repressed vimentin expression in vitro. Additionally, TACC-3 knockdown simulated the inhibiting effect of lnc-PCTST overexpression on PC cell lines, and the impaired proliferation, invasion effect and E-cadherin, vimentin expression on lnc-PCTST over-expressed cell lines can be rescued by overexpressed TACC-3. Significantly, the expression of lnc-PCTST was closely associated with its genomic neighboring gene TACC-3 and inhibited its promoter activity. In conclusion, lnc-PCTST is a potential tumor suppressor in PC, which inhibits cell proliferation, invasion, tumorigenesis and EMT by modulating TACC-3.

摘要

胰腺癌(PC)是最致命的恶性肿瘤之一,也是一项重大的健康负担,尽管目前治疗有进展,但预后仍很差。许多长链非编码RNA(lncRNA)已被证明对PC的肿瘤发生和进展至关重要。然而,lnc-PCTST的确切表达模式及其临床意义仍不清楚。本研究采用微阵列共阵列方法研究lnc-PCTST及其相关mRNA在三对PC组织和相邻非肿瘤组织中的表达模式。简而言之,我们的数据表明lnc-PCTST在PC组织中表达下调。此外,lnc-PCTST已被证明与转化酸性卷曲螺旋3(TACC-3)的表达呈负相关。在对48对癌组织中的34对进行qRT-PCR验证后,这种表达模式得到了进一步证实。此外,在PC细胞系中过表达lnc-PCTST可在体外抑制细胞增殖和侵袭,并在体内抑制肿瘤发生(以裸鼠为动物模型),但不改变细胞迁移。此外,lnc-PCTST过表达在体外增加了E-钙黏蛋白并抑制了波形蛋白的表达。此外,敲低TACC-3模拟了lnc-PCTST过表达对PC细胞系的抑制作用,而过表达TACC-3可以挽救lnc-PCTST过表达细胞系中受损的增殖、侵袭作用以及E-钙黏蛋白、波形蛋白的表达。值得注意的是,lnc-PCTST的表达与其基因组邻近基因TACC-3密切相关,并抑制其启动子活性。总之,lnc-PCTST是PC中一种潜在的肿瘤抑制因子,它通过调节TACC-3来抑制细胞增殖、侵袭、肿瘤发生和上皮-间质转化。

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