Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, P.R. China.
Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, P.R. China.
Oncol Rep. 2018 Aug;40(2):1093-1102. doi: 10.3892/or.2018.6462. Epub 2018 May 24.
Recent studies have revealed that overexpression of long non‑coding RNA (lncRNA) PVT1 is correlated with several types of cancer. However, its role in pancreatic cancer development remains to be clarified. In the present study, we found that PVT1 promoted the growth and the epithelial‑mesenchymal transition (EMT) of pancreatic cancer cells. We first determined that PVT1 was upregulated in pancreatic cancer tissues compared with adjacent normal tissues. Knockdown of PVT1 inhibited viability, adhesion, migration and invasion. Furthermore, PVT1 knockdown reduced the expression of mesenchymal markers including Snail, Slug, β‑catenin, N‑cadherin and vimentin, while it increased epithelial marker expression of E‑cadherin. Finally, knockdown of PVT1 inhibited the TGF‑β/Smad signaling, including p‑Smad2/3 and TGF‑β1 but enhanced the expression of Smad4. In contrast, overexpression of PVT1 reversed the process. These findings revealed that PVT1 acts as an oncogene in pancreatic cancer, possibly through the regulation of EMT via the TGF‑β/Smad pathway and PVT1 may serve as a potential target for diagnostics and therapeutics in pancreatic cancer.
最近的研究表明，长链非编码 RNA (lncRNA) PVT1 的过表达与多种类型的癌症有关。然而，其在胰腺癌发展中的作用仍需阐明。在本研究中，我们发现 PVT1 促进了胰腺癌细胞的生长和上皮-间充质转化（EMT）。我们首先确定 PVT1 在胰腺癌组织中的表达高于相邻正常组织。PVT1 的敲低抑制了细胞活力、黏附、迁移和侵袭。此外，PVT1 的敲低降低了间充质标志物包括 Snail、Slug、β-catenin、N-钙黏蛋白和波形蛋白的表达，同时增加了上皮标志物 E-钙黏蛋白的表达。最后，PVT1 的敲低抑制了 TGF-β/Smad 信号通路，包括 p-Smad2/3 和 TGF-β1，但增强了 Smad4 的表达。相反，PVT1 的过表达逆转了这一过程。这些发现表明，PVT1 在胰腺癌中作为一种癌基因发挥作用，可能通过 TGF-β/Smad 通路调节 EMT，并且 PVT1 可能成为胰腺癌诊断和治疗的潜在靶点。
