Zhang Weijie, Chen Jun, Li Yue, Zhang Ruochen, Wang Anqi, Zeng Yuanyuan, Zhu Jianjie, Liu Zeyi, Huang Jian-An
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Suzhou Key Laboratory for Respiratory Diseases, Suzhou, 215006, China.
J Cancer. 2022 Jul 18;13(10):2988-2999. doi: 10.7150/jca.72789. eCollection 2022.
Circular RNAs (circRNAs) are shown to play a significant role in cancer initiation and progression by interacting on microRNAs (miRNAs) which act as one kind of competing endogenous RNAs (ceRNAs) for the regulation effect on target gene expressions. This study was performed to explore the prognosis-related circRNAs in lung adenocarcinoma (LUAD) patients by integrated analysis and find the mechanism it worked. The miRNAs and mRNAs, accompanied with circRNAs expressions were obtained through The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, The cytoHubba app of Cytoscape was used to identify hubgenes. Quantitative real-time PCR (q-RT PCR) was performed to identify the expression of circRNA, miRNA and mRNA, Cell Counting Kit-8 (CCK-8) and clone formation assays were used to evaluate the proliferation ability of different kinds of cells in vitro. Transwell assays were utilized to assess the motility of tumor cells. Finally, circRNA_0039908/let7c-5p/RRM2 axis was identified in our research, it can play an important role in the LUAD pathogenesis progression and we found that the proliferation, invasion and migration abilities of LUAD cells can be suppressed after knockdown of circRNA_0039908. This work indicates that circRNA_0039908/let7c-5p/RRM2 axis may be a promising target in the prognosis and treatment of LUAD patients. Circ_0039908/miR-let-7c/RRM2 axis can promote the ability of proliferation, migration and invasion of LUAD cells.
环状RNA（circRNAs）已被证明通过与微小RNA（miRNAs）相互作用，在癌症的发生和发展中发挥重要作用。miRNAs作为一种竞争性内源性RNA（ceRNAs），对靶基因表达具有调控作用。本研究旨在通过综合分析探索肺腺癌（LUAD）患者中与预后相关的circRNAs，并找出其作用机制。通过癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获得了miRNAs、mRNAs以及circRNAs的表达数据，利用Cytoscape的cytoHubba应用程序鉴定枢纽基因。采用定量实时PCR（q-RT PCR）鉴定circRNA、miRNA和mRNA的表达，使用细胞计数试剂盒-8（CCK-8）和克隆形成试验评估不同类型细胞在体外的增殖能力。利用Transwell试验评估肿瘤细胞的运动能力。最后，在我们的研究中鉴定出了circRNA_0039908/let7c-5p/RRM2轴，它在LUAD发病机制进展中起重要作用，并且我们发现敲低circRNA_0039908后，LUAD细胞的增殖、侵袭和迁移能力受到抑制。这项工作表明circRNA_0039908/let7c-5p/RRM2轴可能是LUAD患者预后和治疗的一个有前景的靶点。Circ_0039908/miR-let-7c/RRM2轴可促进LUAD细胞的增殖、迁移和侵袭能力。
