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外泌体传递的 circ_0004664 通过 miR-942-5p 调控 PTEN 表达抑制镉转化的人支气管上皮细胞的迁移和侵袭。

Exosome-transmitted circ_0004664 suppresses the migration and invasion of cadmium-transformed human bronchial epithelial cells by regulating PTEN expression via miR-942-5p.

机构信息

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.

出版信息

Chem Biol Interact. 2024 Nov 1;403:111221. doi: 10.1016/j.cbi.2024.111221. Epub 2024 Sep 3.

Abstract

Exosomes play a crucial role in regulating extracellular communication between normal and cancer cells within the tumor microenvironment, thereby affecting tumor progression through their cargo molecules. However, the specific impact of exosomal circular RNAs (circRNAs) on the development of cadmium-induced carcinogenesis remains unclear. To address this, we investigated whether exosomes derived from normal human bronchial epithelial BEAS-2B (N-B2B) cells could transmit circRNA to cadmium-transformed BEAS-2B (Cd-B2B) cells and the potential effects on Cd-B2B cells. Our findings demonstrated a significant downregulation of circ_0004664 in Cd-B2B cells compared to N-B2B cells (P < 0.01). Overexpression of circ_0004664 in Cd-B2B cells led to a significant inhibition of cell migration and invasion (P < 0.01 or P < 0.05). Furthermore, N-B2B cells could transfer circ_0004664 into recipient Cd-B2B cells via exosomes, subsequently inhibiting cell migration and invasion (P < 0.05 or P < 0.01). Mechanistic investigations revealed that exosomal circ_0004664 functioned as a competitive endogenous RNA for miR-942-5p, resulting in an upregulation of PTEN (P < 0.05). Our study highlights the involvement of exosomal circ_0004664 in cell-cell communication during cadmium carcinogenesis, providing a novel insight into the role of exosomal circRNA in this process.

摘要

外泌体在调节肿瘤微环境中正常细胞和癌细胞之间的细胞外通讯方面发挥着关键作用,从而通过其携带的分子影响肿瘤的进展。然而,外泌体环状 RNA(circRNA)对镉诱导致癌作用的具体影响尚不清楚。为了解决这一问题,我们研究了来自正常人类支气管上皮 BEAS-2B(N-B2B)细胞的外泌体是否可以将 circRNA 传递给镉转化的 BEAS-2B(Cd-B2B)细胞,以及对 Cd-B2B 细胞的潜在影响。我们的研究结果表明,与 N-B2B 细胞相比,Cd-B2B 细胞中的 circ_0004664 显著下调(P<0.01)。在 Cd-B2B 细胞中过表达 circ_0004664 导致细胞迁移和侵袭显著抑制(P<0.01 或 P<0.05)。此外,N-B2B 细胞可以通过外泌体将 circ_0004664 转移到受体 Cd-B2B 细胞中,随后抑制细胞迁移和侵袭(P<0.05 或 P<0.01)。机制研究表明,外泌体 circ_0004664 作为 miR-942-5p 的竞争性内源性 RNA 发挥作用,导致 PTEN 上调(P<0.05)。我们的研究强调了外泌体 circ_0004664 在镉致癌过程中细胞间通讯中的作用,为外泌体 circRNA 在这一过程中的作用提供了新的见解。

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