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长链非编码 RNA AK021443 促进肝纤维化的作用。

Effect of long non‑coding RNA AK021443 on promoting hepatic fibrosis .

机构信息

Clinical Laboratory of Zunyi Maternity and Child Health Care Hospital, Zunyi, Guizhou 563000, P.R. China.

Department of Blood Transfusion, Zunyi Maternity and Child Health Care Hospital, Zunyi, Guizhou 563000, P.R. China.

出版信息

Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11835. Epub 2021 Jan 26.

DOI:10.3892/mmr.2021.11835
PMID:33495828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7821357/
Abstract

Long non‑coding (lnc)RNAs serves an important role in the occurrence and development of hepatic fibrosis. lncRNA AK021443 is highly expressed in hepatocellular carcinoma (HCC) and promotes HCC cell proliferation, invasion and migration. The present study aimed to investigate the effect of AK021443 on hepatic fibrosis. AK021443 was overexpressed in the human LX‑2 hepatic stellate cell (HSC) line using a plasmid to observe its effect on hepatic fibrosis . A Cell Counting Kit‑8 assay was performed to assess cell proliferation, whereas cell cycle distribution and related proteins were analyzed via flow cytometry and western blotting, respectively. The protein expression levels of epithelial‑mesenchymal transition (EMT)‑associated and extracellular matrix (ECM) proteins were also analyzed via western blotting. Immunofluorescence was conducted to observe the generation of collagen1, and the activity of inflammatory factors and reactive oxygen species (ROS) was also analyzed. Compared with the pcDNA group, AK021443 overexpression significantly promoted cell proliferation, enhanced the transition of cells from G to S phase and increased the expression of cyclin‑dependent kinase 2 and cyclin D1, but reduced the p21 protein expression levels. In addition, EMT capabilities, ECM deposition and the generation of collagen1 were increased by AK021443 overexpression compared with the pcDNA group. Moreover, AK021443 overexpression significantly increased the release of inflammatory cytokines, including TGF‑β, interleukin‑1β, platelet derived growth factor, epidermal growth factor and ROS, compared with the pcDNA group. In conclusion, the present study suggested that AK021443 overexpression increased HSC proliferation, activation and the proinflammatory response, indicating the potential role of AK02144 in aggravating hepatic fibrosis.

摘要

长链非编码 RNA(lncRNA)在肝纤维化的发生和发展中起着重要作用。lncRNA AK021443 在肝细胞癌(HCC)中高度表达,促进 HCC 细胞增殖、侵袭和迁移。本研究旨在探讨 AK021443 对肝纤维化的影响。通过质粒过表达 AK021443 观察其对肝纤维化的影响。使用细胞计数试剂盒-8 法评估细胞增殖,通过流式细胞术分析细胞周期分布和相关蛋白,通过 Western blot 分析上皮-间充质转化(EMT)相关和细胞外基质(ECM)蛋白的表达水平。通过 Western blot 观察胶原 1 的生成,分析炎症因子和活性氧(ROS)的活性。与 pcDNA 组相比,AK021443 过表达显著促进细胞增殖,增强细胞从 G1 期向 S 期的转化,增加周期蛋白依赖性激酶 2 和周期蛋白 D1 的表达,但降低 p21 蛋白的表达水平。此外,与 pcDNA 组相比,AK021443 过表达增加了 EMT 能力、ECM 沉积和胶原 1 的生成。此外,与 pcDNA 组相比,AK021443 过表达显著增加了炎症细胞因子的释放,包括 TGF-β、白细胞介素-1β、血小板衍生生长因子、表皮生长因子和 ROS。综上所述,本研究表明 AK021443 过表达增加了 HSC 的增殖、激活和促炎反应,表明 AK021443 在加重肝纤维化中具有潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/0d10e7e2a9d4/mmr-23-03-11835-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/9d1bd0c7c899/mmr-23-03-11835-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/a8a52130ad53/mmr-23-03-11835-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/102a5d1da796/mmr-23-03-11835-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/2076c84fe688/mmr-23-03-11835-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/89121b62b598/mmr-23-03-11835-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/0d10e7e2a9d4/mmr-23-03-11835-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/9d1bd0c7c899/mmr-23-03-11835-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/a8a52130ad53/mmr-23-03-11835-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/102a5d1da796/mmr-23-03-11835-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/2076c84fe688/mmr-23-03-11835-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/89121b62b598/mmr-23-03-11835-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322f/7821357/0d10e7e2a9d4/mmr-23-03-11835-g05.jpg

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The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma.纤维化和肝相关成纤维细胞在肝细胞癌发病机制中的作用。
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