Activation of circ_0072088/miR-1261/PIK3CA pathway accelerates lung adenocarcinoma progression

被引:6
作者
Cao, Feng [1 ]
Liu, Sihua [2 ]
Li, Ziyi [2 ]
Meng, Lingjiao [2 ]
Sang, Meixiang [2 ]
Shan, Baoen [2 ]
机构
[1] Hebei Med Univ, Hosp 4, Dept Radiat Oncol, Shijiazhuang, Hebei, Peoples R China
[2] Hebei Med Univ, Hosp 4, Res Ctr, Shijiazhuang 050017, Hebei, Peoples R China
关键词
bioinformatics; cell lines; circRNAs; lung adenocarcinoma; tumorigenesis; RNA;
D O I
10.1111/1759-7714.14369
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Circular RNAs (circRNAs) are involved in the tumorigenesis and progression of lung adenocarcinoma (LUAD). This study aimed to determine the role of circ_0072088 in LUAD. Methods The existence and expression of circ_0072088 in human LUAD tissues and cell lines were determined through Sanger sequencing, quantitative reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization (FISH). Subsequently, the biological role of circ_0072088 was examined using loss-of-function assays in H1299 cells. Moreover, circ_0072088/miR-1261/PIK3CA pathway-mediated biological effects in H1299 were verified using bioinformatic prediction and experiments, including interaction analysis (FISH, luciferase reporter, and RNA-pulldown assays), and tumor biological function test (CCK8 and colony formation, wound healing, and transwell assays). Finally, miR-1261 and PIK3CA expression and LUAD patient survival were further analyzed using FISH, immunohistochemical staining, and the Kaplan-Meier plotter database, respectively. Results First, an increase in circ_0072088 was confirmed in human LUAD tissues. Thereafter, it was mainly localized in the cytoplasm and was found to enhance cell proliferation, migration, and invasion of H1299 cells. Mechanistically, circ_0072088 directly downregulated miR-1261 expression, whereas increased PIK3CA gene expression was associated with poor overall survival of LUAD patients. The activation of the circ_0072088/miR-1261/PIK3CA regulatory pathway may play a significant role in the tumorigenesis and progression of LUAD. Conclusions Circ_0072088-dependent regulation of miR-1261/PIK3CA is important for cell proliferation, migration, and invasion during the tumorigenesis and progression of LUAD, warranting the need to consider the circ_0072088/miR-1261/PIK3CA regulatory pathway as a potential therapeutic target in patients with lung adenocarcinoma.
引用
收藏
页码:1548 / 1557
页数:10
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