CircRNA_104889 promotes lung adenocarcinoma cell invasion via sponging miR4458
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PRIMARY RESEARCH
Cancer Cell International Open Access
CircRNA_104889 promotes lung adenocarcinoma cell invasion via sponging miR4458 Yongyong Yan1,2†, Jiantian Yang1,3†, Janak L. Pathak1,2†, Haiyan Wang1, Jun Zha1, Yongxiang Wei1, Haibo Tang4* and Linhu Ge1,2*
Abstract Background: Lung 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. Methods: In 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. Results: CircRNA 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. Conclusions: CircRNA_104889 promotes lung adenocarcinoma cell migration and invasion by sponging miR4458 and targeting ERK1/2 signaling and caspase-3 expression. Keywords: Lung adenocarcinoma, CircRNA, Cancer cell invasion, MiRNA sponging, ERK1/2 pathway, Caspase-3
*Correspondence: [email protected]; [email protected] † Yongyong Yan, Jiantian Yang, Janak L. Pathak equally contributed to this study and share the first authorship 2 Institute of Oral Disease, Guangzhou Medical University, 39 Huangsha Road, Guangzhou 510140, China 4 Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, 13 Shiliugang Road, Guangzhou 510000, China Full list of author information is available at the end of the article
Background Lung adenocarcinoma is the most common pathological cancer with a high mortality rate [1]. Lung cancer is mainly categorized as small cell and non-small cell lung cancer (NSCLC). Pulmonary adenocarcinoma and pulmonary squamous cell carcinoma are the two main types of NSCLC. Around 85% of lung cancers are NSCLC, and pulmonary adenocarcinoma is the most common NSCLC [2]. Although cancer treatment strategies have been improved, the survival rate of overall lung cancer is only 19% [3]. Mult
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