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

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 in vitro 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 in vivo, 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 in vivo and in vitro. Mechanistic investigations also revealed that circ_0085539 could sponge miR-526b-5p and that miR526b-5p could directly target SERP1. The cytological experiments in vitro 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.

Graphical Abstract

Abstract

This study is the first to investigate the effect of the interactions between circ_0085539, miR-526b-5p, and SERP1 in OS. The authors found that circ_0085539 accelerated OS progression by binding to and regulating miR-526b-5p, which suppressed SERP1. Their findings also revealed a novel molecular interactome of circ_0085539/miR-526b-5p/SERP1 in OS.