Overexpression of hsa_circ_0061817 Can Inhibit the Proliferation and Invasion of Lung Cancer Cells Based on Active Compounds

Overexpression of hsa_circ_0061817 Can Inhibit the Proliferation and Invasion of Lung Cancer Cells Based on Active Compounds
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基于活性化合物的hsa_circ_0061817过表达可抑制肺癌细胞的增殖和侵袭

DOI:
10.1155/2022/4509019
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发表时间:
2022-09
影响因子:
--
通讯作者:
Zhou Xiangdong
Zhou Xiangdong
中科院分区:
生物学2区
文献类型:
--
作者:
Ye Longping;Zhong Youqing;Hu Lihua;Huang Ya;Tang Xiang;Yu Shanjun;Huang Jianxin;Wang Ziyuan;Li Qi;Zhou Xiangdong

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目的研究hsa_circ_0061817在肺腺癌细胞中的表达水平及其对细胞增殖和侵袭的影响,探讨hsa_circ_0061817在肺腺癌中的作用机制。方法将hsa_circ_0061817过表达质粒(OE-hsacirc_0061817)分别转染人肺A549细胞和小鼠LLC-LUC细胞。CCK-8法检测细胞活力,细胞克隆形成实验和EdU法检测细胞增殖。Transwell实验检测细胞侵袭能力,流式细胞仪检测细胞凋亡。WB法检测凋亡、上皮间质转化(EMT)相关蛋白及靶蛋白的表达,观察OE-hsa_circ_0061817对A549细胞裸鼠移植瘤生长的影响。利用生物信息学方法预测hsa_circ_0061817的结合microRNA(miRNA),构建竞争性内源RNA(ceRNA)调控网络,并对miRNA靶基因进行功能分析。结果与PLO-ciR组相比,OE-hsa_circ_00061817组A549和LLC-LUC细胞的存活率、增殖能力和侵袭能力均明显降低,而凋亡率明显增加。WB结果显示caspase 3、caspase 7、caspase 9和E-cadherin的表达明显增加,而vimentin和N-cadherin的表达明显降低。最重要的是,OE-hsa_circ_00061817抑制了携带A549肿瘤的裸鼠的生长。根据TargetScan和mirBase数据库,hsa_circ_0061817可以竞争性结合hsa_mir-181 b-3 p、hsa-mir-337- 3 p、hsa-mir-421和hsa-mir-548 d-3 p。功能富集结果表明,miRNA靶基因参与了多种肿瘤相关的生物学过程,包括细胞凋亡的负调控、基因表达、肿瘤转录失衡、转化生长因子-β、P53信号通路等。结论hsa_circ_0061817过表达可抑制肺腺癌A549和LLC-LUC细胞的增殖,可能通过减弱EMT过程降低肺腺癌细胞的侵袭能力,为肺腺癌的防治提供了新的靶点。
Objective This study was aimed at investigating the expression level of hsa_circ_0061817 in lung adenocarcinoma cells and its effect on cell proliferation and invasion and the possible mechanism of hsa_circ_0061817 in lung adenocarcinoma. Methods The overexpression plasmids of hsa_circ_0061817 (OE-hsacirc_0061817) were transfected into human lung A549 cells and mouse LLC-LUC cells, respectively. The cell viability was detected by CCK-8, and the cell proliferation was detected by cell clone formation assay and EdU assay. Transwell test was used to detect the ability of cell invasion, and apoptosis was detected by flow cytometry. WB was applied to determine the expression of apoptosis and epithelial mesenchymal transition- (EMT-) related proteins and also target proteins for observation the effect of OE-hsa_circ_0061817 on the growth of A549 cells in nude mice. Bioinformatics method was used to predict the binding microRNA (miRNA) of hsa_circ_0061817 and construct the regulatory network of competitive endogenous RNA (ceRNA) and functional analysis of miRNA target genes. Results Compared with PLO-ciR group, the cell viability, proliferation, and invasive ability of A549 and LLC-LUC were significantly reduced in OE-hsa_circ_00061817 group, while the apoptosis increased in OE-hsa_circ_00061817 group compared to PLO-ciR group. WB results showed that the expression of caspase 3, caspase 7, caspase 9, and E-cadherin increased significantly, while the expression levels of vimentin and N-cadherin decreased severely. Most importantly, OE-hsa_circ_00061817 inhibited the growth of A549 tumor-bearing nude mice. According to TargetScan and mirBase databases, hsa_circ_0061817 may competitively bind hsa_mir-181b-3p, hsa-mir-337-3p, hsa-mir-421, and hsa-mir-548d-3p. The results of functional enrichment showed that miRNA target genes were involved in many cancer-related biological processes, including negative regulation of apoptosis, gene expression, transcriptional imbalance in cancer, transforming growth factor-β, and P53 signal pathway. Conclusions Over expression of hsa_circ_0061817 inhibits the proliferation of lung adenocarcinoma A549 and LLC-LUC cells and may reduce the invasive ability of lung adenocarcinoma cells by weakening the process of EMT, which provides a new target for the prevention and treatment of lung adenocarcinoma.
DOI: 10.1016/j.biopha.2021.111805
发表时间: 2021-06-11
影响因子: 7.5
作者:
Ghafouri-Fard, Soudeh;Dinger, Marcel E.;Hajiesmaeili, Mohammadreza
通讯作者: Hajiesmaeili, Mohammadreza
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发表时间: 2021-01-08
影响因子: 14.9
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DOI: 10.3389/fimmu.2021.719175
发表时间: 2021
影响因子: 7.3
作者:
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通讯作者: Yan Y
DOI: 10.1186/s12943-022-01582-0
发表时间: 2022-05-05
期刊: MOLECULAR CANCER
影响因子: 37.3
作者:
Xue, Chen;Li, Ganglei;Zheng, Qiuxian;Gu, Xinyu;Bao, Zhengyi;Lu, Juan;Li, Lanjuan
通讯作者: Li, Lanjuan
DOI: --
发表时间: 2021
期刊: Journal of B.U.ON. : official journal of the Balkan Union of Oncology
影响因子: --
作者:
M. Kong;Haijun Chen
通讯作者: M. Kong;Haijun Chen