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circ_0008797 通过海绵吸附 miR-301a-3p/SOCS2 来抑制非小细胞肺癌的增殖、转移和有氧糖酵解。

circ_0008797 attenuates non-small cell lung cancer proliferation, metastasis, and aerobic glycolysis by sponging miR-301a-3p/SOCS2.

机构信息

Department of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, China.

出版信息

Environ Toxicol. 2022 Jul;37(7):1697-1710. doi: 10.1002/tox.23518. Epub 2022 Mar 19.

DOI:10.1002/tox.23518
PMID:35305058
Abstract

PURPOSE

This paper firstly reported the exact function of circ_0008797 on non-small cell lung cancer (NSCLC) progression.

METHODS

NSCLC tissues/matched normal tissues were harvested from 88 NSCLC patients. RNA fluorescence in situ hybridization experiment was applied to detect circ_0008797 localization in NSCLC cells. circ_0008797 effect on NSCLC cells proliferation, migration, invasion, glucolysis, and apoptosis was researched by cell counting kit-8 assay, 5-ethynyl-2'deoxyuridine assay, Transwell experiment, glycolysis assay, and TUNEL assay. Dual luciferase reporter gene assay, RNA pull-down assay and RNA immunoprecipitation assay were used to verify the binding relationship between two genes. In vivo tumorigenesis and lung metastasis was performed using nude mice. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and western blot were applied for genes expression detection. Hematoxylin and eosin staining was performed on lung tissues.

RESULTS

circ_0008797 was low expressed in NSCLC tissues and cell lines, associating with poor outcome (p <.05). circ_0008797 was mainly expressed in NSCLC cells cytoplasm. circ_0008797 inhibited proliferation, migration, invasion, and glycolysis, but enhanced apoptosis of NSCLC cells (p <.05). circ_0008797 attenuated malignant phenotype of NSCLC cells by sponging miR-301a-3p. circ_0008797 facilitated SOCS2 expression by sponging miR-301a-3p. SOCS2 knockdown partially reversed the inhibitory effect of miR-301a-3p inhibition on NSCLC cells malignant phenotype (p <.05). circ_0008797 attenuated NSCLC prolifearion and metastasis in vivo (p <.05).

CONCLUSION

circ_0008797 attenuates NSCLC proliferation, metastasis and aerobic glycolysis by sponging miR-301a-3p/SOCS2.

摘要

目的

本文首次报道了 circ_0008797 对非小细胞肺癌(NSCLC)进展的确切作用。

方法

从 88 例 NSCLC 患者中采集 NSCLC 组织/配对正常组织。应用 RNA 荧光原位杂交实验检测 NSCLC 细胞中 circ_0008797 的定位。通过细胞计数试剂盒-8 测定、5-乙炔基-2'-脱氧尿苷测定、Transwell 实验、糖酵解测定和 TUNEL 测定研究 circ_0008797 对 NSCLC 细胞增殖、迁移、侵袭、糖酵解和凋亡的影响。双荧光素酶报告基因测定、RNA 下拉测定和 RNA 免疫沉淀测定用于验证两个基因之间的结合关系。使用裸鼠进行体内肿瘤发生和肺转移。应用定量逆转录-聚合酶链反应、免疫组织化学和 Western blot 检测基因表达。对肺组织进行苏木精和伊红染色。

结果

circ_0008797 在 NSCLC 组织和细胞系中低表达,与不良预后相关(p<.05)。circ_0008797 主要在 NSCLC 细胞的细胞质中表达。circ_0008797 抑制 NSCLC 细胞的增殖、迁移、侵袭和糖酵解,但增强了其凋亡(p<.05)。circ_0008797 通过海绵吸附 miR-301a-3p 来减弱 NSCLC 细胞的恶性表型。circ_0008797 通过海绵吸附 miR-301a-3p 促进 SOCS2 的表达。SOCS2 敲低部分逆转了 miR-301a-3p 抑制对 NSCLC 细胞恶性表型的抑制作用(p<.05)。circ_0008797 减弱了 NSCLC 细胞在体内的增殖和转移(p<.05)。

结论

circ_0008797 通过海绵吸附 miR-301a-3p/SOCS2 来减弱 NSCLC 的增殖、转移和有氧糖酵解。

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