Geng Qianqian, Zhao Huijie, Zhou Zhiqing, Chen Xiuyuan, Zhao Honglin, Chen Nanzheng, Li Yu, Guo Chunfang, Yang Aimin, Beer David G, Chen Guoan
Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Surgery, University of Michigan, Ann Arbor, USA.
School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Life Sci. 2023 May 1;320:121560. doi: 10.1016/j.lfs.2023.121560. Epub 2023 Mar 7.
Circular RNAs are widely expressed in various cancers and play important roles in tumorigenesis and tumor progression. The function and mechanism of circSMARCA5 in lung adenocarcinoma however remains unclear.
QRT-PCR analysis was applied for determining circSMARCA5 expression in lung adenocarcinoma patient tumor tissues and cells. Molecular biological assays were used for investigating the role of circSMARCA5 in lung adenocarcinoma progression. Luciferase reporter and bioinformatics assays were used for identifying the underlying mechanism.
In this study, we observed that circSMARCA5 expression was decreased in lung adenocarcinoma tissues but silencing of circSMARCA5 in lung adenocarcinoma cells inhibited cell proliferation, colony formation, migration and invasion. Mechanistically, we found EGFR, c-MYC and p21 were down-regulated upon circSMARCA5 knockdown. MiR-17-3p efficiently down- regulated EGFR expression via directly binding to EGFR mRNA.
These studies suggest that circSMARCA5 functions as an oncogene via targeting miR-17-3p-EGFR axis and may represent a promising therapeutic target for lung adenocarcinoma.
环状RNA在多种癌症中广泛表达,并在肿瘤发生和肿瘤进展中发挥重要作用。然而,circSMARCA5在肺腺癌中的功能和机制仍不清楚。
应用QRT-PCR分析来确定circSMARCA5在肺腺癌患者肿瘤组织和细胞中的表达。采用分子生物学实验研究circSMARCA5在肺腺癌进展中的作用。利用荧光素酶报告基因和生物信息学实验来确定潜在机制。
在本研究中,我们观察到circSMARCA5在肺腺癌组织中的表达降低,但在肺腺癌细胞中沉默circSMARCA5可抑制细胞增殖、集落形成、迁移和侵袭。机制上,我们发现circSMARCA5敲低后,表皮生长因子受体(EGFR)、c-MYC和p21下调。MiR-17-3p通过直接结合EGFR mRNA有效下调EGFR表达。
这些研究表明,circSMARCA5通过靶向miR-17-3p-EGFR轴发挥癌基因作用,可能是肺腺癌有前景的治疗靶点。