Abstract
BackgroundLung adenocarcinoma is metastatic cancer with a high mortality rate. Circular RNAs (circRNAs) are a type of noncoding RNA and play a vital role in cancer progression. However, the expression and function of circRNAs in lung adenocarcinoma are still mostly unknown.MethodsIn this study, we screened the differential expression of circRNAs in human bronchial epithelial cells (HBE) and A549 human lung adenocarcinoma cell line (A549) by human circRNA microarray and RT-qPCR. The role of overexpressed circRNA_104889 in A549 cell proliferation, apoptosis, migration, and invasion was studied extensively. Intracellular localization of circRNA_104889 was visualized by FISH assay. MiRNA sponging, ERK1/2 signaling, and caspase-3 expression were analyzed in siRNA-mediated circRNA_104889 knockdowned A549 cells.ResultsCircRNA microarray showed overexpression of circRNA_104889 (> 13-fold) in A459 cells compared to HBE. This finding was further corroborated by the RT-qPCR result. CircRNA_104889 was mainly localized in the cytoplasm of A549 cells. The knockdown of circRNA_104889 in A549 cells by si-RNA mediated RNA interference did not affect cell proliferation and apoptosis but significantly inhibited cell migration and invasion in vitro. Furthermore, knockdown of circRNA_104889 led to an increase of miR4458 expression. Overexpression of miR4458 inhibited A549 cell migration. Both the knockdown of circRNA_104889 and overexpression of miR4458 inhibited the caspase-3 expression and ERK1/2 phosphorylation in A549 cells.ConclusionsCircRNA_104889 promotes lung adenocarcinoma cell migration and invasion by sponging miR4458 and targeting ERK1/2 signaling and caspase-3 expression.
Highlights
Lung adenocarcinoma is metastatic cancer with a high mortality rate
General profile of circRNA microarray CircRNA microarray test analyzed the differential expressions of circRNA in A549 human lung adenocarcinoma cell line (A549) and human bronchial epithelial cells (HBE) cells
The results showed 966 upregulated and 272 downregulated circRNAs in A549 cells compared to HBE
Summary
Lung adenocarcinoma is metastatic cancer with a high mortality rate. The expression and function of circRNAs in lung adenocarcinoma are still mostly unknown. Lung adenocarcinoma is the most common pathological cancer with a high mortality rate [1]. Around 85% of lung cancers are NSCLC, and pulmonary adenocarcinoma is the most common NSCLC [2]. Cancer treatment strategies have been improved, the survival rate of overall lung cancer is only 19% [3]. Multiple factors such as late-stage diagnosis, Yan et al Cancer Cell Int (2020) 20:432 drug resistance, and metastasis cause poor cancer prognosis and high mortality. It is crucial to explore the molecular mechanisms of lung adenocarcinoma metastasis to unravel the cost-effective diagnostic and therapeutic markers
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