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环状 RNA hsa_circ_0072309 通过调控 miR-607/FTO 轴促进非小细胞肺癌的发生和侵袭。

Circular RNA hsa_circ_0072309 promotes tumorigenesis and invasion by regulating the miR-607/FTO axis in non-small cell lung carcinoma.

机构信息

Department of General Surgery, Changzhou Seventh People's Hospital, Changzhou 213011, Jiangsu, China.

Department of General Surgery, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou 213011, Jiangsu, China.

出版信息

Aging (Albany NY). 2021 Apr 20;13(8):11629-11645. doi: 10.18632/aging.202856.

DOI:10.18632/aging.202856
PMID:33879631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8109101/
Abstract

Emerging evidence has demonstrated that circular RNAs (circRNAs) are abnormally expressed in non-small cell lung carcinoma (NSCLC). However, the contributions of circRNAs to the tumorigenesis of lung adenocarcinoma (LUAD), one of the subtypes of NSCLC, remain unclear. Based on a microarray assay, we found that hsa_circ_0072309 was significantly upregulated in NSCLC compared with matched normal samples. Moreover, functional experiments demonstrated that hsa_circ_0072309 promotes the proliferation, migration, and invasion of NSCLC cells. precipitation of circRNAs, luciferase reporter assays, and biotin-coupled microRNA capture assays were carried out to investigate the mechanisms by which hsa_circ_0072309 regulates NSCLC. Through the above work, we found that hsa_circ_0072309 interacted with miR-607 via its miRNA response element to upregulate the expression of FTO, an m6A demethylase and downstream target of miR-607, thus promoting tumorigenesis of NSCLC. In total, our findings indicated the oncogenic role of hsa_circ_0072309 in NSCLC and provide a potential target for treatment.

摘要

越来越多的证据表明,环状 RNA(circRNAs)在非小细胞肺癌(NSCLC)中表达异常。然而,circRNAs 对 NSCLC 的一个亚型——肺腺癌(LUAD)的肿瘤发生的贡献仍不清楚。基于微阵列分析,我们发现 hsa_circ_0072309 在 NSCLC 中与匹配的正常样本相比明显上调。此外,功能实验表明 hsa_circ_0072309 促进了 NSCLC 细胞的增殖、迁移和侵袭。通过沉淀 circRNAs、荧光素酶报告基因实验和生物素偶联 miRNA 捕获实验,我们研究了 hsa_circ_0072309 调节 NSCLC 的机制。通过上述工作,我们发现 hsa_circ_0072309 通过其 miRNA 反应元件与 miR-607 相互作用,从而上调 m6A 去甲基酶和 miR-607 的下游靶标 FTO 的表达,从而促进 NSCLC 的肿瘤发生。总之,我们的研究结果表明 hsa_circ_0072309 在 NSCLC 中具有致癌作用,并为治疗提供了一个潜在的靶点。

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