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七氟醚通过调控circ-PI4KA抑制结肠癌细胞恶性增殖。

Sevoflurane Suppresses Colon Cancer Cell Malignancy by Regulating circ-PI4KA.

作者信息

Sun Suqing, Wang Peng, Ren Lijie, Wang Hongli, Zhan Yanli, Shan Shimin

机构信息

Department of Anesthesia, Tianjin Fifth Central Hospital, Tianjin, People's Republic of China.

出版信息

Onco Targets Ther. 2021 May 20;14:3319-3333. doi: 10.2147/OTT.S295552. eCollection 2021.

Abstract

PURPOSE

To explore the effect of SEV on colon cancer cells through circ-PI4KA.

METHODS

The RNA level of circular RNA_0062389, microRNA-331-3p and LIM and SH3 protein 1 was determined by quantitative real-time polymerase chain reaction. Protein expression was detected by Western blot. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide, cell colony formation and 5-ethynyl-29-deoxyuridine assays. Cell apoptosis was demonstrated using Annexin V-fluorescein isothiocyanate/propidium iodide double staining assay. Cell migration and invasion were detected by transwell assay. The target relationship between miR-331-3p and circ-PI4KA or LASP1 was predicted by starBase v2.0 online database, and identified by a dual-luciferase reporter assay. The effects between SEV treatment and circ-PI4KA knockdown on tumor formation were presented by in vivo tumor formation assay.

RESULTS

Circ-PI4KA and LASP1 expressions were dramatically upregulated, while miR-331-3p was downregulated in colon cancer tissues and cells, respectively. SEV exposure significantly decreased the expression of circ-PI4KA and LASP1, but increased miR-331-3p expression. SEV inhibited cell proliferation, migration and invasion, and induced cell apoptosis by regulating circ-PI4KA. Furthermore, circ-PI4KA interacted with miR-331-3p, and miR-331-3p interacted with LASP1. SEV inhibited tumor growth by controlling circ-PI4KA in vivo.

CONCLUSION

Circ-PI4KA attenuated SEV-treated colon cancer cell malignancy by upregulating LASP1 through binding to miR-331-3p, which provided a new mechanism for studying surgery-mediated therapy of colon cancer.

摘要

目的

通过circ-PI4KA探讨七氟醚(SEV)对结肠癌细胞的影响。

方法

采用定量实时聚合酶链反应测定环状RNA_0062389、微小RNA-331-3p和LIM与SH3蛋白1的RNA水平。通过蛋白质免疫印迹法检测蛋白表达。采用3-(4,5)-二甲基噻唑-2,5-二苯基四氮唑溴盐、细胞集落形成和5-乙炔基-2'-脱氧尿苷检测法研究细胞增殖。使用膜联蛋白V-异硫氰酸荧光素/碘化丙啶双染法证明细胞凋亡。通过Transwell检测法检测细胞迁移和侵袭。通过starBase v2.0在线数据库预测miR-331-3p与circ-PI4KA或LASP1之间的靶标关系,并通过双荧光素酶报告基因检测法进行鉴定。通过体内肿瘤形成试验呈现SEV处理和circ-PI4KA敲低对肿瘤形成的影响。

结果

circ-PI4KA和LASP1的表达在结肠癌组织和细胞中分别显著上调,而miR-331-3p下调。SEV暴露显著降低circ-PI4KA和LASP1的表达,但增加miR-331-3p的表达。SEV通过调节circ-PI4KA抑制细胞增殖、迁移和侵袭,并诱导细胞凋亡。此外,circ-PI4KA与miR-331-3p相互作用,且miR-331-3p与LASP1相互作用。SEV在体内通过控制circ-PI4KA抑制肿瘤生长。

结论

circ-PI4KA通过与miR-331-3p结合上调LASP1,从而减弱SEV处理的结肠癌细胞的恶性程度,这为研究手术介导的结肠癌治疗提供了一种新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b751/8144176/a88e13de8481/OTT-14-3319-g0001.jpg

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