Circular RNA hsa_circ_0008003 promotes the progression of non–small‐cell lung cancer by sponging miR‐548I and regulating KPNA4 expression

Abstract Objective The study aimed to explore the effect of circ_0008003 on the progression of non–small‐cell lung cancer (NSCLC) and its underlying regulation mechanism. Methods Expression of hsa_circ_0008003, miRNA (miR)‐548I and karyopherin subunit α 4 (KPNA4) was examined by quantitative real‐ti...

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Bibliographic Details
Main Authors: Wenshu Yang, Yingying Yao, Shuai Yang, Yaoqi Ke
Format: Article
Language:English
Published: Wiley 2023-02-01
Series:Thoracic Cancer
Subjects:
Online Access:https://doi.org/10.1111/1759-7714.14777
Description
Summary:Abstract Objective The study aimed to explore the effect of circ_0008003 on the progression of non–small‐cell lung cancer (NSCLC) and its underlying regulation mechanism. Methods Expression of hsa_circ_0008003, miRNA (miR)‐548I and karyopherin subunit α 4 (KPNA4) was examined by quantitative real‐time polymerase chain reaction. Cell viability and proliferation ability were detected by cell counting kit‐8 assay and 5‐ethynyl‐2′‐deoxyuridine assay, respectively. Flow cytometry was performed to monitor cell apoptosis. Western blot assay was used to evaluate the protein levels of KPNA4, Bax, and Bcl‐2. Cell migration and invasion were assessed by transwell assays. The targeted relationship between miR‐548I and hsa_circ_0008003 or KPNA4 was confirmed by dual‐luciferase reporter and RNA immunoprecipitation assays. Furthermore, the role of hsa_circ_0008003 in vivo was investigated by xenograft assay. Results Circ_0008003 expression was increased in NSCLC tissues and cell lines. Circ_0008003 knockdown reduced cell viability, migration, invasion, angiogenesis, and caused apoptosis in NSCLC cells. Moreover, miR‐548I was targeted by circ_0008003, and miR‐548I knockdown reversed the influence of circ_0008003 silence on NSCLC progression. KPNA4 was targeted by miR‐548I, and miR‐548I overexpression suppressed cell viability, migration, invasion, angiogenesis, and promoted cell apoptosis via decreasing KPNA4. In addition, circ_0008003 regulated KPNA4 expression via miR‐548I. Circ_0008003 knockdown decreased NSCLC cell growth in the xenograft model. Conclusion Circular RNA hsa_circ_0008003 promoted progression in NSCLC by sponging miR‐548I and regulating KPNA4 expression, hinting that circ_0008003 participates in NSCLC pathogenesis.
ISSN:1759-7706
1759-7714