Circ_0058058通过微RNA-557依赖的PDL1调控驱动胰腺癌的恶性表型和免疫逃逸。
Circ_0058058 Drives the Malignant Phenotypes and Immune Evasion of Pancreatic Cancer by the MicroRNA-557-Dependent Regulation of PDL1.
发表日期:
作者:
Lin Lin, Liang Xiao, Chang'e Jin, Ying Qin, Haoyuan Deng, Meixiang Li, Huan Lin, Xuehao Gong
来源:
Cellular & Molecular Immunology
摘要:
胰腺癌(PC)是世界上最致命的恶性肿瘤之一。最近研究表明,环状RNA在PC进程中起着关键作用。然而,circ_0058058在PC中的功能鲜为人知。用定量实时聚合酶链反应检测了circ_0058058、microRNA-557-5p(miR-557)和程序化细胞死亡受体配体1(PDL1)的表达。通过功能实验揭示了circ_0058058缺陷对PC细胞增殖、凋亡、侵袭、血管生成和免疫逃逸的影响。通过双荧光素酶报告基因实验和RNA免疫沉淀实验确定了miR-557与circ_0058058或PDL1之间的结合关系。通过体内实验揭示了circ_0058058沉默对肿瘤形成的影响。Circ_0058058在PC组织和细胞系中高度表达。circ_0058058的沉默抑制了PC细胞的增殖、侵袭、血管生成和免疫逃逸,同时促进凋亡。机械方面,circ_0058058作为miR-557的分子海绵调节PDL1的表达。此外,circ_0058058在体内对肿瘤生长具有促进作用。我们的研究表明,circ_0058058作为miR-557海绵上调PDL1的表达,从而引发PC的增殖、侵袭、血管生成和免疫逃逸。版权所有©2023 Wolters Kluwer Health,Inc.。保留所有权利。
Pancreatic cancer (PC) is one of the most deadly malignancies in the world. Recently, circular RNAs play crucial roles in PC progression. However, the functions of circ_0058058 in PC are barely known.The expression of circ_0058058, microRNA-557-5p (miR-557), and programmed cell death receptor ligand 1 (PDL1) was detected by quantitative real-time polymerase chain reaction. Functional experiments were implemented to disclose the effect of circ_0058058 deficiency on PC cell proliferation, apoptosis, invasion, angiogenesis, and immune escape. The binding relationship between miR-557 and circ_0058058 or PDL1 was identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo assay was used to disclose the impact of circ_0058058 silencing on tumor formation in vivo.Circ_0058058 was highly expressed in PC tissues and cell lines. Knockdown of circ_0058058 repressed cell proliferation, invasion, angiogenesis, and immune escape while contributed to apoptosis in PC cells. Mechanically, circ_0058058 worked as a molecular sponge of miR-557 to regulate PDL1 expression. Moreover, circ_0058058 showed a promotional effect on tumor growth in vivo.Our findings suggested that circ_0058058 served as miR-557 sponge to upregulate PDL1, thereby triggering PC proliferation, invasion, angiogenesis, and immune escape.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.