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Circ_0078767通过吸附miR-665调控GPX3表达来抑制非小细胞肺癌进展。

Circ_0078767 Inhibits the Progression of Non-Small-Cell Lung Cancer by Regulating the GPX3 Expression by Adsorbing miR-665.

作者信息

Liu Xiting, Chen Ze, Wu Yuqiang, Gu Feng, Yan Dong, Yang Lei, Ma Qin, Fu Caihong

机构信息

Department of Respiratory Oncology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China.

Department of Radiology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China.

出版信息

Int J Genomics. 2022 Mar 17;2022:6361256. doi: 10.1155/2022/6361256. eCollection 2022.

Abstract

Non-small-cell lung cancer (NSCLC) is one of the most serious cancers. The circular RNA_0078767 (circ_0078767) expression was decreased in NSCLC tissues. However, the molecular mechanism of circ_0078767 remains unknown. The expression of circ_0078767, microRNA-665 (miR-665), and glutathione peroxidase 3 (GPX3) was detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Cell proliferation, migration, and invasion were detected by colony formation assay and transwell assay, respectively. The lactate production and glucose consumption were tested by glycolysis. Western blot examined the protein levels of hexokinase-2 (HK2), matrix metalloproteinase-9 (MMP9), and GPX3 cells. Circinteractome predicted the relationship between miR-665 and circ_0078767 or GPX3 and was verified by dual luciferase reporter assays. The xenotransplantation model was established to study the role of circ_0078767 in vivo. The expression of circ_0078767 and GPX3 was decreased in NSCLC tissues, while the expression of miR-665 was increased. Circ_0078767 can sponge miR-665, and GPX3 is the target of miR-665. In vitro complement experiments showed that knockdown of circ_0078767 significantly promoted malignant behavior of NSCLC, while cotransfection of miR-665 inhibitor partially reduced this change. In addition, the GPX3 overexpression decreased the promoting effects of miR-665 upregulation on proliferation, migration, and invasion of NSCLC cells. Mechanically, circ_0078767 regulates the GPX3 expression in NSCLC cells by spongy miR-665. In addition, in vivo studies have shown that downregulation of circ_0078767 promotes tumor growth. Circ_0078767 silencing promotes proliferation, migration, invasion, and glycolysis of NSCLC cells by regulating the miR-665/GPX3 axis, suggesting that circ_0078767/miR-665/GPX3 axis may be a potential regulatory mechanism for the treatment of NSCLC.

摘要

非小细胞肺癌(NSCLC)是最严重的癌症之一。环状RNA_0078767(circ_0078767)在NSCLC组织中的表达降低。然而,circ_0078767的分子机制仍不清楚。通过定量实时荧光聚合酶链反应(qRT-PCR)检测circ_0078767、微小RNA-665(miR-665)和谷胱甘肽过氧化物酶3(GPX3)的表达。分别通过集落形成试验和Transwell试验检测细胞增殖、迁移和侵袭。通过糖酵解检测乳酸产生和葡萄糖消耗。蛋白质印迹法检测己糖激酶-2(HK2)、基质金属蛋白酶-9(MMP9)和GPX3细胞的蛋白质水平。Circinteractome预测miR-665与circ_0078767或GPX3之间的关系,并通过双荧光素酶报告基因试验进行验证。建立异种移植模型以研究circ_0078767在体内的作用。circ_0078767和GPX3在NSCLC组织中的表达降低,而miR-665的表达增加。Circ_0078767可以吸附miR-665,且GPX3是miR-665的靶标。体外补充实验表明,敲低circ_0078767可显著促进NSCLC的恶性行为,而共转染miR-665抑制剂可部分减轻这种变化。此外,GPX3过表达降低了miR-665上调对NSCLC细胞增殖、迁移和侵袭的促进作用。机制上,circ_0078767通过吸附miR-665调节NSCLC细胞中GPX3的表达。此外,体内研究表明,circ_0078767的下调促进肿瘤生长。Circ_0078767沉默通过调节miR-665/GPX3轴促进NSCLC细胞的增殖、迁移、侵袭和糖酵解,提示circ_0078767/miR-665/GPX3轴可能是治疗NSCLC的潜在调控机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d20/8948607/a769242624e9/IJG2022-6361256.001.jpg

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