hsa_circRNA_001587 upregulates SLC4A4 expression to inhibit migration, invasion, and angiogenesis of pancreatic cancer cells via binding to microRNA-223
hsa_circRNA_001587 upregulates SLC4A4 expression to inhibit migration, invasion, and angiogenesis of pancreatic cancer cells via binding to microRNA-223
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DOI：
10.1152/ajpgi.00118.2020
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发表时间：
2020-12-01
影响因子：
4.5
通讯作者：
Du, Lei
中科院分区：
文献类型：
--
作者：
Zhang, Xiutian;Tan, Peng;Du, Lei
张旭，谭平，庄勇，杜磊，hsa_CircRNA_001587通过与microRNA结合抑制胰腺癌细胞的迁移、侵袭和血管生成，上调SLC4A4的表达，从而抑制胰腺癌细胞的迁移、侵袭和血管生成。于2020年9月2日首次出版；doi：10.1152/ajpgi.00118.2020。胰腺癌是一种难于诊断和治疗的恶性肿瘤。环状RNA(CircRNAs)是可用于诊断某些癌症或作为癌症治疗靶点的生物标志物。本研究旨在探讨人环状核糖核酸001587(HsA_CircRNA_001587)在前列腺癌发生发展中的作用及其机制。RT-qPCR检测hSA_CircRNA_001587和microRNA223(miR-223)在PC组织和细胞中的表达。通过双荧光素酶报告基因分析、RNApulldown、ArgAerte2(AGO2)免疫沉淀实验和Northern印迹分析，验证了hSA_CircRNA_001587、miR-223与溶质载体家族4成员4(SLC4A4)之间的结合关系。进一步分析了它们在PC细胞系PANC-1中的作用。此外，我们还通过体外转染法下调或上调了hSA_CircRNA_001587、miR-223和SLC4A4的表达。建立小鼠PC细胞异种移植模型，评价肿瘤的体内生长情况。HSA_CircRNA_001587在PC组织和细胞系中低表达，而miR-223在PC组织和细胞系中高表达。HSA_CircRNA_001587上调下调基质金属蛋白酶-2和-9、微染色体维持2和血管内皮生长因子的表达，降低PC细胞的增殖、迁移、侵袭、血管生成和致瘤能力。能与hsa_CircRNA_001587结合的mir-223逆转了hsa_CircRNA_001587对PC细胞的作用。此外，SLC4A4被确定为miR-223的靶点，它的敲除可以抵消hsa_CircRNA_001587过表达对PC细胞的调控作用或抑制miR-223的表达。因此，hSA_CircRNA_001587通过抑制miR-223介导的SLC4A4抑制而抑制PC细胞的迁移、侵袭、血管生成和肿瘤的发生。在胰腺癌(PC)细胞中，新发现的值得注意的人类环状(HSA_CIRC)RNA_001587和溶质载体家族4成员(SLC4A4)低表达，而microRNA(MiR)R-223高表达。人血清白蛋白环状RNA 001587与miR-223结合。HSA_CircRNA_001587过表达可抑制PC进展。MiR-223过表达下调SLC4A4的表达，促进PC细胞生长。HsA_CircRNA_001587可能是PC治疗的潜在靶点。
Zhang X, Tan P, Zhuang Y, Du L. hsa_circRNA_001587 upregulates SLC4A4 expression to inhibit migration, invasion, and angiogenesis of pancreatic cancer cells via binding to microRNA Am J Physiol Gastrointest Liver Physiol 319: G703-G717, 2020. First published September 2, 2020; doi:10.1152/ajpgi.00118.2020. Pancreatic cancer (PC) is a malignant tumor that is difficult to diagnose and treat. Circular RNAs (circRNAs) are biomarkers that may be used to diagnose certain cancers or act as targets for cancer treatment. We aimed to explore the functions of human circular RNA 001587 (hsa_circRNA_001587) on the progression of PC and the underlying mechanism. The expression pattern of hsa_circRNA_001587 and microRNA-223 (miR-223) in PC tissues and cells was determined by RT-qPCR. Dual-luciferase reporter gene assay, RNApulldown, Argonaute 2 (AGO2) immunoprecipitation assay, and Northern blot analysis were applied to verify the binding relationships among hsa_circRNA_001587, miR-223 and solute carrier family 4 member 4 (SLC4A4). Further analysis of their roles was performed in PC cell line PANC-1. Moreover, we either downregulated or upregulated the expression of hsa_circRNA_001587, miR-223, and SLC4A4 by transfection in vitro. A mouse xenograft model of PC cells was established to evaluate tumor growth in vivo. hsa_circRNA_001587 was poorly expressed, but miR-223 was highly expressed in PC tissues and cell lines. Upregulation of hsa_circRNA_001587 downregulated the expression of matrix metalloproteinase-2 and-9, minichromosome maintenance 2, and vascular endothelial growth factor, and decreased the proliferation, migration, invasion, angiogenic and tumorigenic abilities of PC cells. MiR-223, which can bind with hsa_circRNA_001587, reversed the effects of hsa_circRNA_001587 on PC cells. In addition, SLC4A4 was identified as a target of miR-223, and its knockdown could counteract the regulatory effects of overexpressed hsa_circRNA_001587 or inhibited miR-223 expression on PC cells. Therefore, hsa_circRNA_001587 inhibits PC cell migration, invasion, angiogenesis and tumorigenesis by impairing miR-223-mediated SLC4A4 inhibition.NEW & NOTEWORTHY Human circular (hsa_circ)RNA_001587 and solute carrier family 4 member 4 (SLC4A4) are poorly expressed but microRNA (miR)R-223 is overexpressed in pancreatic cancer (PC) cells. hsa_circRNA_001587 binds to miR-223. Overexpression of hsa_circRNA_001587 inhibits PC progression. Overexpression of miR-223 downregulates the expression of SLC4A4 and promotes PC cell growth. hsa_circRNA_001587 may be a potential target for PC treatment.