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环状RNA CircCDYL通过吸附miR-185-5p并上调TNRC6A来调节非小细胞肺癌细胞的增殖和凋亡。

Circular RNA CircCDYL Regulates Proliferation and Apoptosis in Non-Small Cell Lung Cancer Cells by Sponging miR-185-5p and Upregulating TNRC6A.

作者信息

Bian Wei-Xin, Xue Feng, Wang Li-Yan, Xing Xiao-Fang

机构信息

Department of Oncology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang Province 150001, People's Republic of China.

Department of Oncology, Affiliated Hospital of Guilin Medical College, Guilin, Guangxi Province 541001, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Jan 25;13:633-642. doi: 10.2147/CMAR.S280315. eCollection 2021.

Abstract

AIM

A series of research reveal that circular RNA (circRNA) plays a vital role in regulating the development of tumor cells. In this research, we would explore the role and mechanism of circCDYL in non-small cell lung cancer (NSCLC).

METHODS

RT-PCR was performed to detect the expression of circCDYL in NSCLC tissues, plasma, and cell lines. The tumor cell proliferation ability was evaluated by clone formation assay, and cell cycle determination. Flow cytometry was used to detect apoptosis in NSCLC cell lines. Western blot and RT-PCR were used to assess the expression of proteins and genes. Luciferase assay was performed to confirm the relationship of circRNA-miRNA-mRNA.

RESULTS

The decreased level of circCDYL was observed in NSCLC patients' tissues and plasma, which was also downregulated in NSCLC cell lines. Forced expression of circCDYL inhibited cell viability, proliferation and induced apoptosis in A549 cells. Luciferase assay verified that circCDYL could bind with miR-185-5p and confirmed that TNRC6A was a downstream target of miR-185-5p. Overexpression of miR-185-5p or silencing of TNRC6A could inhibit the anti-tumor effect of circCDYL in A549 cells via regulating the ERK1/2 signal.

CONCLUSION

Here, we revealed that circCDYL inhibited proliferation and induced apoptosis in NSCLC cell lines via regulating ERK1/2 signal, and the mechanism of this progression may target miR-185-5p/TNRC6A, which provided a theoretical basis for clinical therapy.

摘要

目的

一系列研究表明,环状RNA(circRNA)在调节肿瘤细胞的发展中起着至关重要的作用。在本研究中,我们将探索circCDYL在非小细胞肺癌(NSCLC)中的作用及机制。

方法

采用逆转录聚合酶链反应(RT-PCR)检测circCDYL在NSCLC组织、血浆及细胞系中的表达。通过克隆形成试验和细胞周期测定评估肿瘤细胞增殖能力。采用流式细胞术检测NSCLC细胞系中的细胞凋亡情况。利用蛋白质免疫印迹法(Western blot)和RT-PCR评估蛋白质和基因的表达。进行荧光素酶报告基因检测以确认circRNA-微小RNA(miRNA)-信使核糖核酸(mRNA)之间的关系。

结果

在NSCLC患者的组织和血浆中观察到circCDYL水平降低,在NSCLC细胞系中也呈下调状态。circCDYL的过表达抑制了A549细胞的活力、增殖并诱导其凋亡。荧光素酶报告基因检测证实circCDYL可与miR-185-5p结合,并确认TNRC6A是miR-185-5p的下游靶点。miR-185-5p的过表达或TNRC6A的沉默可通过调节细胞外信号调节激酶1/2(ERK1/2)信号抑制circCDYL在A549细胞中的抗肿瘤作用。

结论

在此,我们揭示了circCDYL通过调节ERK1/2信号抑制NSCLC细胞系的增殖并诱导其凋亡,这一过程的机制可能靶向miR-185-5p/TNRC6A,为临床治疗提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fb/7846864/71783b786511/CMAR-13-633-g0001.jpg

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