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环状 DNA 结合蛋白 2D 通过调控 miR-130b-3p/丝氨酸苏氨酸激酶 11 轴抑制 PD-L1 介导的非小细胞肺癌转移和免疫逃逸。

CircDENND2D Inhibits PD-L1-Mediated Non-Small Cell Lung Cancer Metastasis and Immune Escape by Regulating miR-130b-3p/STK11 Axis.

机构信息

Department of Respiratory and Critical Care Medicine, Hainan Affiliated Hospital of Hainan Medical University/Hainan General Hospital, Haikou, 570311, Hainan Province, People's Republic of China.

Department of Thoracic Surgery, Hainan Affiliated Hospital of Hainan Medical University/Hainan General Hospital, Haikou, 570311, Hainan Province, People's Republic of China.

出版信息

Biochem Genet. 2023 Dec;61(6):2691-2709. doi: 10.1007/s10528-023-10401-0. Epub 2023 May 24.

Abstract

Local recurrence and distant metastasis of non-small cell lung cancer (NSCLC) caused by immune escape is one of the root causes of treatment difficulties. We aim to investigate the mechanism of immune escape in NSCLC. NSCLC tissues were collected. Cell proliferation was detected by CCK-8 assay. Cell migration and invasion ability was measured by Transwell assay. The expressions of E-cadherin, N-cadherin and PD-L1 were detected by Western blot. NSCLC cells were co-cultured with CD8 T cells to simulate tumor microenvironment in vitro. The proportion of CD8 T cells and apoptosis were detected by flow cytometry. Dual-luciferase reporter gene assay confirmed the targeting relationship of circDENND2D and STK11. The expressions of circDENND2D and STK1 were down-regulated, while miR-130b-3p expression was up-regulated in NSCLC tissues. Overexpression of circDENND2D or STK11 inhibited NSCLC cells proliferation, migration and invasion, and attenuated the immune escape of NSCLC cells. CircDENND2D targeted miR-130b-3p to competitively promote STK11 expression. STK11 knockdown or miR-130b-3p overexpression attenuated the function of circDENND2D overexpression on NSCLC cells. CircDENND2D inhibited metastasis and immune escape of NSCLC by regulating miR-130b-3p/STK11 axis.

摘要

非小细胞肺癌(NSCLC)的免疫逃逸导致的局部复发和远处转移是治疗困难的根本原因之一。我们旨在研究 NSCLC 免疫逃逸的机制。收集 NSCLC 组织。通过 CCK-8 检测细胞增殖。通过 Transwell 检测细胞迁移和侵袭能力。通过 Western blot 检测 E-cadherin、N-cadherin 和 PD-L1 的表达。将 NSCLC 细胞与 CD8 T 细胞共培养,在体外模拟肿瘤微环境。通过流式细胞术检测 CD8 T 细胞的比例和凋亡。双荧光素酶报告基因实验证实 circDENND2D 和 STK11 之间的靶向关系。NSCLC 组织中 circDENND2D 和 STK1 的表达下调,而 miR-130b-3p 的表达上调。circDENND2D 或 STK11 的过表达抑制 NSCLC 细胞增殖、迁移和侵袭,并减弱 NSCLC 细胞的免疫逃逸。circDENND2D 通过竞争性促进 STK11 表达来靶向 miR-130b-3p。STK11 敲低或 miR-130b-3p 过表达减弱了 circDENND2D 过表达对 NSCLC 细胞的功能。CircDENND2D 通过调节 miR-130b-3p/STK11 轴抑制 NSCLC 的转移和免疫逃逸。

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