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环状 RNA circTTBK2 通过 miR-873-5p/TEAD1/DERL1 轴促进非小细胞肺癌恶性进展。

Circular RNA circTTBK2 facilitates non-small-cell lung cancer malignancy through the miR-873-5p/TEAD1/DERL1 axis.

机构信息

Department of General Practice, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, P.R. China.

Department of Respiratory & Critical Care Medicine, Changchun Central Hospital, Changchun, Jilin Province, 130000, P.R. China.

出版信息

Epigenomics. 2022 Aug;14(16):931-949. doi: 10.2217/epi-2021-0480. Epub 2022 Aug 2.

DOI:10.2217/epi-2021-0480
PMID:35916080
Abstract

The underlying mechanisms by which circular RNAs (circRNAs) regulate non-small-cell lung cancer (NSCLC) progression remain elusive. This study investigated the role of circRNA circTTBK2 in NSCLC tumorigenesis. Quantitative reverse transcriptase polymerase chain reaction analysis of circTTBK2 in NSCLC tissues and cell lines was performed. Cell proliferation, migration, invasion and tumorigenesis were confirmed and using CCK-8, EdU incorporation, Transwell assays and xenograft technique. The circTTBK2/miR-873-5p/TEAD1/DERL1 axis was verified by RNA immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assays. Overexpressed circTTBK2 in NSCLC tissues indicates poor prognosis of NSCLC patients. circTTBK2 harbors miR-873-5p, and miR-873-5p directly targets TEAD1. TEAD1 transcriptionally activates DERL1. This study revealed a novel machinery of circTTBK2/miR-873-5p/TEAD1/DERL1 for NSCLC tumorigenesis.

摘要

环状 RNA(circRNAs)调控非小细胞肺癌(NSCLC)进展的潜在机制仍不清楚。本研究探讨了环状 RNA circTTBK2 在 NSCLC 肿瘤发生中的作用。通过定量逆转录聚合酶链反应分析 NSCLC 组织和细胞系中的 circTTBK2。使用 CCK-8、EdU 掺入、Transwell 分析和异种移植技术证实了 circTTBK2 对细胞增殖、迁移、侵袭和肿瘤发生的影响。通过 RNA 免疫沉淀、染色质免疫沉淀和荧光素酶报告基因分析验证了 circTTBK2/miR-873-5p/TEAD1/DERL1 轴。在 NSCLC 组织中过表达的 circTTBK2 表明 NSCLC 患者的预后不良。circTTBK2 含有 miR-873-5p,miR-873-5p 直接靶向 TEAD1。TEAD1 转录激活 DERL1。本研究揭示了 circTTBK2/miR-873-5p/TEAD1/DERL1 调控 NSCLC 肿瘤发生的新机制。

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