Silencing of Long Non-Coding RNA HOTAIR Alleviates Epithelial-Mesenchymal Transition in Pancreatic Cancer via the Wnt/β-Catenin Signaling Pathway.
Silencing of Long Non-Coding RNA HOTAIR Alleviates Epithelial-Mesenchymal Transition in Pancreatic Cancer via the Wnt/β-Catenin Signaling Pathway.
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DOI：
10.2147/cmar.s265578
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发表时间：
2021
影响因子：
3.3
通讯作者：
Shi L
中科院分区：
文献类型：
--
作者：
Tang Y;Song G;Liu H;Yang S;Yu X;Shi L
胰腺癌（PC）是一种预后不良且治疗方案存在争议的恶性肿瘤。长链非编码RNA（lncRNA）是PC发生发展的重要因素。本研究探讨了HOTAIR对PC上皮间质转化（EMT）的可能影响及其相关机制。 PC模型由10mg/100g二甲基苯并蒽(DMBA)在胰腺中诱导。向小鼠注射 HOTAIR 模拟物和 HOTAIR shRNA，以确定 HOTAIR 在 PC 中的作用。随后，测定了PC细胞中HOTAIR的表达。为了确定 HOTAIR 在 PC 中的作用机制，分别用 HOTAIR 模拟物、针对 HOTAIR 的 shRNA、Wnt/b-catenin 激活剂 (LiCl) 和 Wnt/b-catenin 抑制剂 (XAV939) 转染人 PC 细胞系 PANC-1、Miapaca-2 和人正常胰腺导管上皮细胞系 HPDE6-C7。此外，还测定了Wnt/β-catenin信号通路相关基因（β-catenin、cyclinD1、c-myc、LEF-1和c-Jun）的表达以及EMT标志物（E-cadherin、N-cadherin和Vimentin）的水平。最后，通过功能实验评估细胞生物学过程。 HOTAIR被发现在小鼠PC细胞中高表达。在人 PC 细胞系 PANC-1 和 Miapaca-2 中，沉默 HOTAIR 后，β-catenin、cyclinD1、c-myc、LEF-1 和 c-Jun、N-cadherin 和 Vimentin 的表达降低，而 E-cadherin 的表达增加。此外，我们观察到沉默HOTAIR可以抑制Wnt/β-catenin信号通路，从而减轻肿瘤细胞的EMT并抑制细胞增殖、迁移和侵袭的能力。本研究的主要发现是，沉默 HOTAIR 可能通过 Wnt/β-catenin 信号通路抑制 EMT 和 PC 的生长，为 PC 提供一种新的治疗方法。
Pancreatic cancer (PC) is a malignancy with poor prognosis and controversial treatment options. Long non-coding RNA (lncRNA) is a significant factor in the development of PC. In the current study, the possible effects of HOTAIR on the epithelial–mesenchymal transition (EMT) of PC and the related mechanisms were investigated. The PC models were induced by 10 mg/100 g dimethylbenzoanthracene (DMBA) in pancreas. Mice were injected with the HOTAIR mimic and HOTAIR shRNA to determine the role of HOTAIR in PC. Subsequently, the expression of HOTAIR in PC cells was assayed. To determine the mechanism of HOTAIR in PC, human PC cell line PANC-1, Miapaca-2 and human normal pancreatic ductal epithelial cell line HPDE6-C7 were transfected with the HOTAIR mimic, the shRNA against HOTAIR, the Wnt/b-catenin activator (LiCl), and the Wnt/b-catenin inhibitor (XAV939), respectively. Moreover, the expressions of the Wnt/β-catenin signaling pathway-related genes (β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun) and the levels of the EMT markers (E-cadherin, N-cadherin and Vimentin) were determined. Finally, the cell biological processes were evaluated by functional experiments. HOTAIR was found to be highly expressed in the PC cells in mice. The expression of β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun, N-cadherin and Vimentin was found to be decreased, while the expression of E-cadherin was found to be increased subsequent to the silencing of HOTAIR in human PC cell lines PANC-1 and Miapaca-2. Additionally, it was observed that the silencing of HOTAIR could inhibit the Wnt/β-catenin signaling pathway to alleviate EMT of tumor cells and inhibit the capacities of cell proliferation, migration, and invasion. The key finding of the present study is that the silencing of HOTAIR could potentially inhibit EMT and growth of PC through the Wnt/β-catenin signaling pathway, providing a novel therapy for PC.