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环状 RNA circ-PTEN 通过抑制 PTEN 提升非小细胞肺癌细胞的增殖能力。

Circular RNA circ-PTEN elevates PTEN inhibiting the proliferation of non-small cell lung cancer cells.

机构信息

Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, PR China.

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, PR China.

出版信息

Hum Cell. 2021 Jul;34(4):1174-1184. doi: 10.1007/s13577-021-00526-y. Epub 2021 Apr 5.

Abstract

Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor in various cancer types, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) has recently been proven to be strongly linked with cancer progression. Here, we aimed to investigate the biological relevance and clinical significance of circRNA derived from PTEN in NSCLC. We found that circ-PTEN (hsa_circ_0094342) was significantly decreased in NSCLC tissues and serum, which was attributed to the upregulation of RNA-binding protein DHX9. Low circ-PTEN was linked with malignant clinical features and poor outcome. Exogenous expression of circ-PTEN markedly inhibited NSCLC cell proliferation in vitro as well as retarded tumor growth in vivo. Circ-PTEN increased the expression of its host gene PTEN via acting as a sponge for miR-155 and miR-330-3p, leading to the inactivation of the carcinogenic PI3K/AKT signaling pathway. The xenograft tumor model also indicated the existence of circ-PTEN/miR-155/miR-330-3p/PTEN regulatory axis in vivo. Our data for the first time demonstrate that circ-PTEN functions as a tumor-inhibiting circRNA in NSCLC through post-transcriptionally regulating PTEN, hinting a promising diagnostic/prognostic biomarker as well as therapeutic target for NSCLC patients.

摘要

磷酸酶和张力蛋白同源物(PTEN)是多种癌症类型中著名的肿瘤抑制因子,包括非小细胞肺癌(NSCLC)。环状 RNA(circRNA)最近被证明与癌症进展密切相关。在这里,我们旨在研究 NSCLC 中源自 PTEN 的 circRNA 的生物学相关性和临床意义。我们发现,circ-PTEN(hsa_circ_0094342)在 NSCLC 组织和血清中显著降低,这归因于 RNA 结合蛋白 DHX9 的上调。低 circ-PTEN 与恶性临床特征和不良预后相关。外源性表达 circ-PTEN 可显著抑制 NSCLC 细胞在体外的增殖,并在体内抑制肿瘤生长。circ-PTEN 通过作为 miR-155 和 miR-330-3p 的海绵,增加其宿主基因 PTEN 的表达,从而使致癌的 PI3K/AKT 信号通路失活。异种移植肿瘤模型也表明 circ-PTEN/miR-155/miR-330-3p/PTEN 调节轴在体内的存在。我们的数据首次表明,circ-PTEN 通过转录后调节 PTEN 在 NSCLC 中发挥抑癌 circRNA 的作用,提示其作为 NSCLC 患者有前途的诊断/预后生物标志物和治疗靶点。

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