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hsa_circ_0085539 通过调控miR-526b-5p和SERP1促进骨肉瘤进展。

hsa_circ_0085539 Promotes Osteosarcoma Progression by Regulating miR-526b-5p and SERP1.

作者信息

Liu Wei, Wang Dunwei, Wang Xu, Liu Pengcheng, Yan Ming

机构信息

Department of Spine Surgery, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, Jilin 130021, China.

Department of Anesthesiology, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, Jilin 130021, China.

出版信息

Mol Ther Oncolytics. 2020 Oct 4;19:163-177. doi: 10.1016/j.omto.2020.09.009. eCollection 2020 Dec 16.

Abstract

This study aimed to expand the competing endogenous RNA network in osteosarcoma (OS) involving hsa_circ_0085539 and its downstream target miR-526b-5p. The expression levels of circ_0085539, miR-526b-5p, and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA in OS tissues and cells were detected and analyzed by qRT-PCR. After that, the interrelationships between these three genetic materials were validated with a luciferase reporter assay system. The effect of the circ_0085539/miR-526b-5p/SERP1 axis on OS cell malignancy phenotypes was further assessed using assays, including cell counting kit-8 (CCK-8) assays, colony foci formation assays, wound-healing migration assays, and transwell invasion assays. To determine the function of circ_0085539 on OS tumor growth , a xenograft formation assay was performed. In OS tissues and cells, the expression of circ_0085539 and SERP1 was upregulated, while that of miR-526b-5p was downregulated. After experimental analyses, it was found that silencing circ_0085539 inhibited the aggression of OS and . Mechanistic investigations also revealed that circ_0085539 could sponge miR-526b-5p and that miR526b-5p could directly target SERP1. The cytological experiments demonstrated that miR-526b-5p could restore the effect of circ_0085539 in terms of promoting OS malignancy phenotypes by suppressing SERP1. Overall, the present study validated that hsa_circ_0085539 could promote the progression of OS by regulating miR-526b-5p/SERP1.

摘要

本研究旨在扩展骨肉瘤(OS)中涉及hsa_circ_0085539及其下游靶标miR-526b-5p的竞争性内源性RNA网络。通过qRT-PCR检测并分析了OS组织和细胞中circ_0085539、miR-526b-5p和应激相关内质网蛋白1(SERP1)mRNA的表达水平。之后,用荧光素酶报告基因检测系统验证了这三种遗传物质之间的相互关系。使用包括细胞计数试剂盒-8(CCK-8)检测、集落形成检测、伤口愈合迁移检测和Transwell侵袭检测等实验,进一步评估circ_0085539/miR-526b-5p/SERP1轴对OS细胞恶性表型的影响。为了确定circ_0085539对OS肿瘤生长的作用,进行了异种移植形成实验。在OS组织和细胞中,circ_0085539和SERP1的表达上调,而miR-526b-5p的表达下调。经过实验分析,发现沉默circ_0085539可抑制OS的侵袭性。机制研究还表明,circ_0085539可以吸附miR-526b-5p,并且miR-526b-5p可以直接靶向SERP1。细胞学实验表明,miR-526b-5p可以通过抑制SERP1来恢复circ_0085539促进OS恶性表型的作用。总体而言,本研究验证了hsa_circ_0085539可通过调节miR-526b-5p/SERP-1促进OS的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f82/7649436/8272ce3ea46f/fx1.jpg

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