BACKGROUND This study focuses on the lncRNA XIST (X inactive-specific transcript), an lncRNA involved in multiple human cancers, and investigates the functional significance of XIST and the molecular mechanisms underlying the epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC). METHODS Clinical specimens from 25 patients as well as 5 human PC cell lines were analyzed for XIST, YAP, and microRNA(miR)-34a by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. To investigate how XIST influences cell proliferation, invasiveness, and apoptosis in PC, we performed the CCK-8 assays, Transwell assays, and flow cytometry. Luciferase reporter assays, qRT-PCR, and Western blot were applied to prove that miR-34a directly binds to XIST. RESULTS Up-regulation of XIST and Yes associated protein (YAP) and down-regulation of miR-34a were consistently observed in the clinical specimens and PC cell lines. Silencing XIST reduced the expression of YAP and suppressed transforming growth factor (TGF)-β1-induced EMT, while over-expression of XIST increased the expression of YAP and promoted EMT. In addition, inhibition of epidermal growth factor receptor (EGFR) hampered the XIST-promoted EMT. The results from the luciferase reporter assays confirmed that miR-34a directly targets XIST and suggested that XIST regulates cell proliferation, invasiveness, and apoptosis in PC by sponging miR-34a. CONCLUSIONS XIST promotes TGF-β1-induced EMT by regulating the miR-34a-YAP-EGFR axis in PC.

中文翻译：

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长的非编码RNA XIST调节EGF受体，以促进胰腺癌中TGF-β1诱导的上皮-间质转化。

背景技术这项研究的重点是lncRNA XIST（X失活特异性转录物），一种参与多种人类癌症的lncRNA，并研究了XIST的功能意义以及胰腺癌（PC）上皮-间质转化（EMT）的分子机制。 。方法采用定量实时荧光定量PCR（qRT-PCR）和免疫组化技术分析25例患者的临床标本以及5种人类PC细胞系的XIST，YAP和microRNA（miR）-34a。为了研究XIST如何影响PC中细胞的增殖，侵袭性和凋亡，我们进行了CCK-8检测，Transwell检测和流式细胞仪。应用荧光素酶报告基因分析，qRT-PCR和Western印迹法证明miR-34a直接与XIST结合。结果在临床标本和PC细胞系中一致观察到XIST和yes相关蛋白（YAP）的上调以及miR-34a的下调。沉默XIST可以减少YAP的表达并抑制转化生长因子（TGF）-β1诱导的EMT，而XIST的过表达则可以增加YAP的表达并促进EMT。另外，抑制表皮生长因子受体（EGFR）阻碍了XIST促进的EMT。萤光素酶报告基因检测的结果证实miR-34a直接靶向XIST，并暗示XIST通过使miR-34a变海绵来调节PC中的细胞增殖，侵袭性和细胞凋亡。结论XIST通过调节PC机中的miR-34a-YAP-EGFR轴促进TGF-β1诱导的EMT。沉默XIST可以减少YAP的表达并抑制转化生长因子（TGF）-β1诱导的EMT，而XIST的过表达则可以增加YAP的表达并促进EMT。另外，抑制表皮生长因子受体（EGFR）阻碍了XIST促进的EMT。萤光素酶报告基因检测的结果证实miR-34a直接靶向XIST，并暗示XIST通过使miR-34a变海绵来调节PC中的细胞增殖，侵袭性和细胞凋亡。结论XIST通过调节PC机中的miR-34a-YAP-EGFR轴促进TGF-β1诱导的EMT。沉默XIST可以减少YAP的表达并抑制转化生长因子（TGF）-β1诱导的EMT，而XIST的过表达则可以增加YAP的表达并促进EMT。另外，抑制表皮生长因子受体（EGFR）阻碍了XIST促进的EMT。萤光素酶报告基因检测的结果证实miR-34a直接靶向XIST，并暗示XIST通过使miR-34a变海绵来调节PC中的细胞增殖，侵袭性和细胞凋亡。结论XIST通过调节PC机中的miR-34a-YAP-EGFR轴促进TGF-β1诱导的EMT。萤光素酶报告基因检测的结果证实miR-34a直接靶向XIST，并暗示XIST通过使miR-34a变海绵来调节PC中的细胞增殖，侵袭性和细胞凋亡。结论XIST通过调节PC机中的miR-34a-YAP-EGFR轴促进TGF-β1诱导的EMT。萤光素酶报告基因检测的结果证实miR-34a直接靶向XIST，并暗示XIST通过使miR-34a变海绵来调节PC中的细胞增殖，侵袭性和细胞凋亡。结论XIST通过调节PC机中的miR-34a-YAP-EGFR轴促进TGF-β1诱导的EMT。