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外泌体递送的 circSATB2 通过靶向 miR-330-5p/PEAK1 轴来调节肺癌细胞的增殖、迁移和侵袭。

Exosome-delivered circSATB2 targets the miR-330-5p/PEAK1 axis to regulate proliferation, migration and invasion of lung cancer cells.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China.

Department of Thoracic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.

出版信息

Thorac Cancer. 2022 Nov;13(21):3007-3017. doi: 10.1111/1759-7714.14652. Epub 2022 Sep 23.

Abstract

Exosomes can carry various kinds of RNAs to mediate intercellular communication. Circular RNA (circRNA) special AT-rich sequence-binding protein 2 (circSATB2) was identified as an oncogene in lung cancer. This study was performed to explore the association of circSATB2 with exosomes and the regulatory mechanism of circSATB2. Exosomes could transmit circSATB2 into lung cancer cells. Exosomes enhanced cell proliferation, invasion, and migration by carrying circSATB2. Exosomal circSATB2 abrogated the inhibitory effect of short hairpin (sh)-circSATB2 on lung cancer progression. Moreover, circSATB2 promoted tumor growth in vivo via exosomes. CircSATB2 interacted with microRNA-330-5p (miR-330-5p) and miR-330-5p targeted pseudopodium enriched atypical kinase 1 (PEAK1). In addition, circSATB2 affected the PEAK1 level via sponging miR-330-5p in lung cancer cells. All results suggested that exosomal transfer of circSATB2 contributed to the malignant development of lung cancer by acting as a sponge of miR-330-5p to upregulate PEAK1.

摘要

外泌体可以携带各种 RNA 来介导细胞间通讯。环状 RNA (circRNA) 富含特殊 AT 序列结合蛋白 2 (circSATB2) 被鉴定为肺癌中的癌基因。本研究旨在探讨 circSATB2 与外泌体的关联及其调控机制。外泌体可以将 circSATB2 传递到肺癌细胞中。外泌体通过携带 circSATB2 增强细胞增殖、侵袭和迁移。外泌体circSATB2 削弱了 sh-circSATB2 对肺癌进展的抑制作用。此外,circSATB2 通过外泌体在体内促进肿瘤生长。circSATB2 与 microRNA-330-5p (miR-330-5p) 相互作用,miR-330-5p 靶向伪足丰富的非典型激酶 1 (PEAK1)。此外,circSATB2 通过在肺癌细胞中海绵吸附 miR-330-5p 来影响 PEAK1 水平。所有结果表明,外泌体转移的 circSATB2 通过作为 miR-330-5p 的海绵来上调 PEAK1,从而促进肺癌的恶性发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e28/9626310/16da10b44c78/TCA-13-3007-g005.jpg

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