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KMID : 1034820230190030453
Molecular & Cellular Toxicology
2023 Volume.19 No. 3 p.453 ~ p.462
CircBLNK regulates tumor proliferation and apoptosis by miR-578/ING5 axis in non-small cell lung cancer
Ping Li

Liuyi Zou
Zuojun Luo
Yuhua Lu
Shuang Yu
Song Jeong-Soo
Yong Xie
Abstract
Background : Non-small cell lung cancer (NSCLC) is one of most threatening malignancies with a high morbidity and mortality that threaten human health and life.

Objective : This study aimed to investigate the role of circBLNK in NSCLC and reveal the regulation mechanism of circBLNK in NSCLC. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the levels of circBLNK, miR-578 and inhibitor of growth 5 (ING5) mRNA. Cell proliferation activity was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2¡¯-deoxyuridine (EdU) staining and colony formation assays. Flow cytometry was carried out to examine cell cycle and cell apoptosis. The dual-luciferase reporter assay was used to validate the interaction between miR-578 and circBLNK or ING5. Xenograft tumor experiment was performed to uncover the function of circBLNK in vivo.

Results : CircBLNK was notably down-regulated in NSCLC tissues and cells. Overexpression of circBLNK suppressed the proliferation and accelerated the apoptosis of NSCLC cells in vitro. CircBLNK targeted miR-578, and circBLNK exerted its biological function in NSCLC cells through sponging miR-578. ING5 was verified as a target of miR-578, and circBLNK increased the abundance of ING5 through targeting miR-578 in NSCLC cells. ING5 interference could partly reverse the biological effects of NSCLC cells mediated by circBLNK overexpression. CircBLNK overexpression repressed NSCLC tumor growth in vivo.

Conclusion : CircBLNK functioned as a tumor suppressor in NSCLC to suppress the proliferation and cell cycle and promote cell apoptosis of NSCLC cells through miR-578/ING5 axis.
KEYWORD
Non-small cell lung cancer, circBLNK, miR-578, ING5, Proliferation, Apoptosis
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