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长链非编码 RNA LUCAT1 通过激活 AKT 磷酸化促进胰腺癌细胞的进展。

The progression of pancreatic cancer cells is promoted by a long non-coding RNA LUCAT1 by activating AKT phosphorylation.

机构信息

Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, PR China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):738-748. doi: 10.26355/eurrev_202101_24635.

DOI:10.26355/eurrev_202101_24635
PMID:33577028
Abstract

OBJECTIVE

In many cancers, long non-coding RNAs (lncRNA) are largely involved; they can regulate cell proliferation, migration, and invasion. However, the research of lncRNA regulation on pancreatic ductal adenocarcinoma is vacant. The aim of this article was to lucubrate the specific role of lncRNA LUCAT1 in regulating the progression of pancreatic cancer.

PATIENTS AND METHODS

Pancreatic cancer and adjacent tissues were collected, and the expression of LUCAT1, one potential involved LucRNA, was measured using real-time qPCR (RT-qPCR). Different pathological types of pancreatic cancer cell lines were cultured, and the expression difference of LncRNA LUCAT1 was detected by RT-qPCR, and two cell lines were selected for downstream experiments. si-RNA was used to knockdown the expression of LUCAT1, comparing the difference in expression of LUCAT1, characterizing cell proliferation by MTT and BrdU staining, detecting apoptosis, and cell cycle changes by flow cytometry. Meanwhile, Western blotting was used for the detection of cyclin expression and thus investigate two important associated signaling pathways. Besides, the expression of signaling pathway was validated by signaling inhibitor.

RESULTS

In comparison to normal cells, LUCAT1 was highly expressed in human pancreatic cancer cell lines (p<0.05). The higher expression of LUCAT1 resulted in enhanced pathogenesis of PDA cells and motivated the development to S phase by regulation of cyclin D1, CDK4. Furthermore, LUCAT1 promoted PDA cells development by inducing AKT's and p38 MAPK's phosphorylation.

CONCLUSIONS

LUCAT1, as the key factor, played a positive role in the proliferation and invasion of pancreatic cells via AKT/MAPK signaling.

摘要

目的

在许多癌症中,长链非编码 RNA(lncRNA)广泛参与其中;它们可以调节细胞增殖、迁移和侵袭。然而,lncRNA 对胰腺导管腺癌的调控研究尚属空白。本文旨在深入研究 lncRNA LUCAT1 在调节胰腺癌进展中的特定作用。

患者和方法

收集胰腺癌及相邻组织,采用实时 qPCR(RT-qPCR)测量潜在涉及的 LucRNA LUCAT1 的表达。培养不同病理类型的胰腺癌细胞系,通过 RT-qPCR 检测 LncRNA LUCAT1 的表达差异,选择两条细胞系进行下游实验。采用 si-RNA 敲低 LUCAT1 的表达,比较 LUCAT1 表达的差异,通过 MTT 和 BrdU 染色检测细胞增殖,通过流式细胞术检测细胞凋亡和细胞周期变化。同时,采用 Western blot 检测细胞周期蛋白的表达,从而研究两条重要的相关信号通路。此外,通过信号抑制剂验证信号通路的表达。

结果

与正常细胞相比,LUCAT1 在人胰腺癌细胞系中高表达(p<0.05)。LUCAT1 的高表达导致 PDA 细胞的发病机制增强,并通过调节细胞周期蛋白 D1、CDK4 促使细胞向 S 期发展。此外,LUCAT1 通过诱导 AKT 和 p38 MAPK 的磷酸化促进 PDA 细胞的发展。

结论

LUCAT1 作为关键因子,通过 AKT/MAPK 信号通路在胰腺细胞的增殖和侵袭中发挥积极作用。

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