长非编码 RNA 通过抑制 Wnt/-catenin 信号通路抑制人胰腺癌细胞 PANC-1 的生长和上皮-间充质转化:来自 和 研究的见解。

Long non-coding RNA suppresses growth and epithelial-mesenchymal transition by inhibiting Wnt/-catenin signaling pathway in human pancreatic cancer PANC-1 cells: Insights from and studies.

机构信息

Department of Endoscopy Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute Shenyang, Liaoning Province China.

出版信息

Acta Pharm. 2024 Mar 30;74(1):131-147. doi: 10.2478/acph-2024-0009. Print 2024 Mar 1.

Abstract

There is increasing evidence that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of malignant tumors, particularly pancreatic cancer. In this study, the influence of the lncRNA on the behavior of human pancreatic cancer cells was investigated with the aim of deciphering its role in growth, migration, and invasion. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate expression in pancreatic cancer cells. Ectopic expression of in PANC-1 cells was induced to evaluate the effects on cell viability and apoptosis, examining the apoptotic genes Bax and Bcl-2. Migration and invasion assays were used to measure the impact of on these cellular processes. studies using a xenograft mouse model examined the effects of on tumor growth, epithelial-to-mesenchymal transition (EMT) markers, and the Wnt/β-catenin signaling pathway. PANC-1 cells showed strikingly low expression compared to other pancreatic cancer cell lines. Ectopic expression reduced the viability of PANC-1 cells primarily by inducing apoptosis, as evidenced by increased Bax and decreased Bcl-2 expression. Overexpression of significantly increased the percentage of apoptotic cells. It also decreased the migration and invasion ability of PANC-1 cells, as demonstrated in wound healing and transwell assays. In addition, overexpression of -suppressed proteins is associated with the Wnt/β-catenin signaling pathway in PANC-1 cells. In the xenograft mouse model, overexpression of inhibited tumor growth, EMT markers, and proteins associated with the Wnt/β-catenin pathway. This study sheds light on the tumour-suppressive role of in PANC-1 cells and suggests its potential as a therapeutic target. These results shed light on the molecular mechanisms underlying the impact of on pancreatic cancer and offer promising opportunities for innovative therapeutic strategies to improve outcomes in this serious malignancy.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在恶性肿瘤的发展和进展中起着至关重要的作用,尤其是胰腺癌。在这项研究中,研究了 lncRNA 对人胰腺癌细胞行为的影响,旨在破译其在生长、迁移和侵袭中的作用。采用实时定量聚合酶链反应(qRT-PCR)检测胰腺癌细胞中 的表达。通过诱导 PANC-1 细胞中 的异位表达,评估其对细胞活力和凋亡的影响,检测凋亡基因 Bax 和 Bcl-2。迁移和侵袭实验用于测量 对这些细胞过程的影响。使用异种移植小鼠模型的 研究检查了 对肿瘤生长、上皮间质转化(EMT)标志物和 Wnt/β-catenin 信号通路的影响。与其他胰腺癌细胞系相比,PANC-1 细胞的 表达明显较低。异位 表达主要通过诱导细胞凋亡降低 PANC-1 细胞的活力,这表现为 Bax 表达增加和 Bcl-2 表达减少。过表达 显著增加了凋亡细胞的百分比。它还降低了 PANC-1 细胞的迁移和侵袭能力,如划痕愈合和 Transwell 实验所示。此外,过表达 抑制了 PANC-1 细胞中与 Wnt/β-catenin 信号通路相关的蛋白表达。在异种移植小鼠模型中,过表达 抑制了肿瘤生长、EMT 标志物和与 Wnt/β-catenin 通路相关的蛋白表达。这项研究揭示了 在 PANC-1 细胞中的肿瘤抑制作用,并表明其作为治疗靶点的潜力。这些结果揭示了 在胰腺癌中的影响的分子机制,并为改善这种严重恶性肿瘤的治疗结果提供了有前途的创新治疗策略的机会。

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