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hsa_circ_0001480 通过调控 miR-363-3p/IBSP 通路影响骨肉瘤的进展。

Hsa_circ_0001480 affects osteosarcoma progression by regulating the miR-363-3p/IBSP pathway.

机构信息

Department of Rehabilitation Medicine, Wuhan Fourth Hospital, Wuhan, Hubei, China.

出版信息

Biotechnol Appl Biochem. 2024 Aug;71(4):721-732. doi: 10.1002/bab.2571. Epub 2024 Feb 26.

Abstract

Osteosarcoma (OS) is a malignant bone tumor that commonly affects young individuals. Circular RNAs (circRNAs) are associated with OS progression. In this study, we aimed to determine the role of hsa_circ_0001480 (circ_0001480) in OS development. OS cell invasion, viability, and colony numbers were assessed via transwell, cell counting kit-8, and colony formation assays, respectively. Tumor growth in vivo was also assessed using an OS mouse model. Additionally, targeted associations among the integrin-binding sialoprotein (IBSP), microRNA (miR)-363-3p, and circ_0001480 were evaluated via RNA immunoprecipitation and dual luciferase reporter assays, whereas their expression levels in OS cells and tissues were determined via quantitative reverse transcription-polymerase chain reaction and western blotting. Loss of circ_0001480 or IBSP significantly inhibited the proliferation and invasion of OS cells, but this effect was reversed by miR-363-3p downregulation. Moreover, circ_0001480 knockdown inhibited neoplasm growth in vivo. circ_0001480 directly bound to miR-363-3p, which further modulated IBSP. Both circ_0001480 and IBSP levels were high, whereas miR-363-3p levels were low in OS cells. Furthermore, low miR-363-3p levels attenuated the suppressive effects of circ_0001480 silencing on the proliferation and invasion of OS cells; however, loss of IBSP partially reversed these effects. Overall, our findings revealed circ_0001480 an oncogenic circRNA stimulating OS progression by modulating the miR-363-3p/IBSP pathway, suggesting its potential for OS treatment.

摘要

骨肉瘤(OS)是一种常见于年轻人的恶性骨肿瘤。环状 RNA(circRNA)与 OS 进展有关。在这项研究中,我们旨在确定 hsa_circ_0001480(circ_0001480)在 OS 发展中的作用。通过 Transwell、细胞计数试剂盒-8 和集落形成测定分别评估 OS 细胞侵袭、活力和集落数量。还使用 OS 小鼠模型评估体内肿瘤生长。此外,通过 RNA 免疫沉淀和双荧光素酶报告基因测定评估整合素结合唾液蛋白(IBSP)、微小 RNA(miR)-363-3p 和 circ_0001480 之间的靶向关联,而通过定量逆转录-聚合酶链反应和 Western印迹测定 OS 细胞和组织中的表达水平。circ_0001480 或 IBSP 的缺失显着抑制 OS 细胞的增殖和侵袭,但 miR-363-3p 下调可逆转该作用。此外,circ_0001480 敲低抑制体内肿瘤生长。circ_0001480 直接与 miR-363-3p 结合,进一步调节 IBSP。OS 细胞中 circ_0001480 和 IBSP 水平较高,而 miR-363-3p 水平较低。此外,miR-363-3p 水平降低减弱了 circ_0001480 沉默对 OS 细胞增殖和侵袭的抑制作用;然而,IBSP 的缺失部分逆转了这些作用。总之,我们的研究结果表明 circ_0001480 通过调节 miR-363-3p/IBSP 通路促进 OS 进展,这表明其在 OS 治疗中的潜力。

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