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

Wenshu Yang, Yingying Yao, Shuai Yang, Yaoqi Ke

Thoracic cancer 2023 Feb

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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. 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. 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. 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. © 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Citation

Wenshu Yang, Yingying Yao, Shuai Yang, Yaoqi Ke. Circular RNA hsa_circ_0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression. Thoracic cancer. 2023 Feb;14(6):544-554