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CircMYC 通过靶向 miR-145/基质金属蛋白酶 2 轴促进小细胞肺癌的增殖、迁移、侵袭和抑制凋亡。

CircMYC promotes proliferation, migration, invasion and inhibits apoptosis of small cell lung cancer by targeting miR-145/ Matrix Metallopeptidase 2 axis.

机构信息

Department of Respiratory and Critical Care Medicine, Taizhou Central Hospital (Taizhou University Hospital), Zhejiang Province, China.

出版信息

Bioengineered. 2022 Apr;13(4):10552-10563. doi: 10.1080/21655979.2022.2062978.

Abstract

Circular RNAs (circRNAs) are involved in the carcinogenesis of lung cancer. Human MYC gene is highly expressed in melanoma, multiple myeloma, and nasopharyngeal carcinoma. We aimed to investigate the role of circMYC in small cell lung cancer (SCLC). The expression of cirMYC in SCLC tissues and cells were examined. Functional studies were performed to evaluate the roles of circMYC in SCLC cells. Luciferase reporter gene assay, RNA pull-down assay, and rescue experiments were performed to evaluate the regulatory relationship between circMYC and miR-145, and MiR-145 and MMP2 mRNA. We found that CirMYC was highly expressed in SCLC tissues and cells. Knockdown of circMYC could inhibit cell proliferation, migration, invasion, and induce apoptosis. CircMYC targeted miR-145 and miR-145 targeted MMP2 (Matrix Metallopeptidase 2) mRNA. Our data indicated that circMYC upregulates the expression of MMP-2 by inhibiting miR-145, which functions to promote the proliferation, migration, and invasion and inhibit the apoptosis of SCLC. These findings suggest that targeting circMYC/miR-145/MMP-2 could serve as a potential therapeutic strategy for SCLC treatment.

摘要

环状 RNA(circRNAs)参与肺癌的发生发展。人类 MYC 基因在黑色素瘤、多发性骨髓瘤和鼻咽癌中高表达。我们旨在研究 circMYC 在小细胞肺癌(SCLC)中的作用。检测 SCLC 组织和细胞中 cirMYC 的表达。进行功能研究以评估 circMYC 在 SCLC 细胞中的作用。进行荧光素酶报告基因检测、RNA 下拉检测和挽救实验,以评估 circMYC 与 miR-145 以及 miR-145 与 MMP2 mRNA 之间的调控关系。我们发现 CirMYC 在 SCLC 组织和细胞中高表达。circMYC 敲低可抑制细胞增殖、迁移和侵袭,并诱导细胞凋亡。CircMYC 靶向 miR-145,而 miR-145 靶向 MMP2(基质金属蛋白酶 2)mRNA。我们的数据表明,circMYC 通过抑制 miR-145 而上调 MMP-2 的表达,从而促进 SCLC 的增殖、迁移和侵袭,并抑制细胞凋亡。这些发现表明,靶向 circMYC/miR-145/MMP-2 可能成为 SCLC 治疗的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb31/9161861/2cf92311c86d/KBIE_A_2062978_UF0001_OC.jpg

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