Abstract

BackgroundCircular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown.MethodsThe levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo.ResultsWe found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1.ConclusionCirc_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

Highlights

  • IntroductionCircular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma

  • Circular RNAs are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma

  • 37 lung adenocarcinoma tissues were collected for RT-qPCR in this study, and results of RT-qPCR suggested that lung adenocarcinoma tissues showed a higher expression of circ_0020850 than that in paired normal tissues (Fig. 1D)

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Summary

Introduction

Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. The function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Lung cancer is one of the foremost reasons for tumorassociated mortality in this world [1]. Current research indicated that circRNA could function as a critical regulator in cancers through sponging microRNA (miRNA) to inhibit miRNA activity and subsequently upregulate target mRNA expression [10, 11]. Circ_0020850 was reported to act as a cancerogenic circRNA in hematological cancers [12] and renal cell carcinoma [13]. The detailed functions of circ_0020850 in lung cancer are lacking. We aimed to investigate the function and regulatory mechanism of circ_0020850 in lung adenocarcinoma

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