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环状 WHSC1 作为一种预后生物标志物,通过 miR-590-5p/SOX5 轴促进非小细胞肺癌的恶性进展。

CircWHSC1 serves as a prognostic biomarker and promotes malignant progression of non-small-cell lung cancer via miR-590-5p/SOX5 axis.

机构信息

Pulmonary and Critical Care Medicine, The People's Hospital of Long hua district, Shenzhen, China.

Pulmonary and Critical Care Medicine, South China Hospital of Shenzhen University, Shenzhen, China.

出版信息

Environ Toxicol. 2023 Oct;38(10):2440-2449. doi: 10.1002/tox.23879. Epub 2023 Jul 7.

DOI:10.1002/tox.23879
PMID:37417879
Abstract

Dysregulated circWHSC1 has been shown to play potential roles in diverse cancer types, including ovarian cancer, endometrial cancer and hepatocellular carcinoma (HCC). The objective of this study was to investigate its expression, underlying role and regulatory mechanism in non-small-cell lung cancer (NSCLC). The expression of circWHSC1 was determined by real-time PCR. After knockdown of circWHSC1 expression in NSCLC cells, the proliferation, migration, and invasion were detected using CCK-8, colony formation, and Transwell assays, and the effects of circWHSC1 on NSCLC tumorigenesis in vivo was also investigated. With the help of luciferase reporter and pull-down assays, we further explored the downstream mechanism of circWHSC1 in NSCLC cells. CircWHSC1 was highly expressed in NSCLC tissues and cell lines. The inhibition of circWHSC1 suppressed the malignant properties of NSCLC cells, as evidenced by the reduction of proliferation, migration and invasion. CircWHSC1 sponged miR-590-5p and functioned as an oncogene in NSCLC by increasing sex determining region Y-boxprotein 5 (SOX5) expression. CircWHSC1 may contribute to the oncogenicity of NSCLC via the regulation of miR-590-5p/SOX5 axis, which might be a novel therapeutic target in NSCLC.

摘要

CircWHSC1 的失调已被证明在多种癌症类型中发挥潜在作用,包括卵巢癌、子宫内膜癌和肝细胞癌(HCC)。本研究旨在探讨其在非小细胞肺癌(NSCLC)中的表达、潜在作用和调控机制。通过实时 PCR 测定 circWHSC1 的表达。在 NSCLC 细胞中敲低 circWHSC1 的表达后,通过 CCK-8、集落形成和 Transwell 测定检测增殖、迁移和侵袭,还研究了 circWHSC1 对 NSCLC 体内肿瘤发生的影响。借助荧光素酶报告和下拉测定,我们进一步探讨了 circWHSC1 在 NSCLC 细胞中的下游机制。CircWHSC1 在 NSCLC 组织和细胞系中高表达。circWHSC1 的抑制抑制了 NSCLC 细胞的恶性特性,表现为增殖、迁移和侵袭减少。CircWHSC1 作为 miRNA-590-5p 的海绵,并通过增加性别决定区 Y 框蛋白 5(SOX5)的表达在 NSCLC 中发挥致癌作用。CircWHSC1 可能通过调节 miR-590-5p/SOX5 轴促进 NSCLC 的致癌性,这可能是 NSCLC 的一种新的治疗靶点。

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