Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China; Department of General Surgery, Daqing Oilfield General Hospital, Daqing, 163000, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin 150086, Heilongjiang Province, China.
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Biomed Pharmacother. 2017 Oct;94:55-62. doi: 10.1016/j.biopha.2017.07.025. Epub 2017 Jul 26.
Extrahepatic cholangiocarcinoma (ECC) is a deadly disease that often responds poorly to conventional chemotherapy or radiotherapy. Long noncoding RNAs (lncRNAs) play important roles in human cancers, including ECC, and recent studies indicated that the lncRNA prostate cancer-associated transcript 1 (non-protein coding) (PCAT1) is involved in multiple cancers. However, the role of PCAT1 in ECC is unclear. Previously, we showed that PCAT1 is up-regulated in both ECC tissue samples and cell lines. Here, we showed that downregulation of PCAT1 following transfection with silencing RNA reduced ECC cell growth and increased cell apoptosis. Additionally, PCAT1 suppression inhibited ECC cell migration and invasion as determined by transwell assay. Furthermore, we determined that PCAT1 is a competing endogenous for microRNA (miR)-122, with bioinformatics analysis and luciferase-reporter assay results demonstrating that PCAT1 regulated WNT1 expression via miR-122. Moreover, PCAT1 downregulation increased levels of glycogen synthase kinase 3β and significantly decreased β-catenin levels in whole cell lysates and nuclear fractions, indicating that PCAT1 silencing inhibited the Wnt/β-catenin-signaling pathway. We also observed that exogenous expression of WNT1 reversed PCAT1-silencing-induced inhibition of ECC cell growth inhibition. These results indicated that PCAT1 silencing inhibited ECC progression by reducing Wnt/β-catenin signaling through miR-122 repression and WNT1 expression. Our findings revealed an important role of PCAT1 in ECC and suggested that PCAT1 might be a potential ECC-related therapeutic target.
肝外胆管癌（ECC）是一种致命的疾病，通常对常规化疗或放疗反应不佳。长链非编码 RNA（lncRNA）在人类癌症中发挥重要作用，包括 ECC，最近的研究表明 lncRNA 前列腺癌相关转录物 1（非蛋白编码）（PCAT1）参与多种癌症。然而，PCAT1 在 ECC 中的作用尚不清楚。先前，我们表明 PCAT1 在 ECC 组织样本和细胞系中均上调。在这里，我们表明转染沉默 RNA 后下调 PCAT1 可降低 ECC 细胞生长并增加细胞凋亡。此外，通过 Transwell 测定，PCAT1 抑制可抑制 ECC 细胞迁移和侵袭。此外，我们确定 PCAT1 是 microRNA（miR）-122 的竞争性内源物，通过生物信息学分析和荧光素酶报告基因测定结果表明，PCAT1 通过 miR-122 调节 WNT1 表达。此外，PCAT1 下调增加了糖原合酶激酶 3β（GSK3β）的水平，并显着降低了整个细胞裂解物和核部分中的 β-连环蛋白水平，表明 PCAT1 沉默抑制了 Wnt/β-连环蛋白信号通路。我们还观察到外源性表达 WNT1 逆转了 PCAT1 沉默诱导的 ECC 细胞生长抑制。这些结果表明，PCAT1 沉默通过抑制 miR-122 抑制和 WNT1 表达来抑制 Wnt/β-连环蛋白信号通路，从而抑制 ECC 进展。我们的研究结果揭示了 PCAT1 在 ECC 中的重要作用，并表明 PCAT1 可能是一种潜在的 ECC 相关治疗靶标。
Zotero 插件