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环状 RNA 0086996 通过 miR-125b-5p 调控骨肉瘤细胞的生长和迁移。

Circular RNA 0086996 regulates growth and migration of osteosarcoma cells via miR-125b-5p.

机构信息

Department of Orthopedic, The 8th Medical Center of Chinese PLA General Hospital, Beijing 100091, China.

Department of Dermatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Pathol Res Pract. 2020 Nov;216(11):153230. doi: 10.1016/j.prp.2020.153230. Epub 2020 Sep 25.

Abstract

Circular RNAs (CircRNAs) have been found to be critical in tumorigenesis; however, the role of CircRNAs in osteosarcoma is to be further studied. In this study, we preliminarily identified the up-expressed CircRNAs and its downstream microRNA in osteosarcoma and investigated its potential regulation mechanism. Hsa_circ_0086996 (Circ_0086996) was found to upregulated in tumor tissue compared to adjacent tissue. Circ_0086996 was significantly overexpressed in osteosarcoma tissue, as well as in osteosarcoma cell lines of SAOS2 and MG-63. Circ_0086996 knockdown significantly suppressed cell proliferation, migration, and invasion. Circ_0086996 knockdown also induced cell cycle arrest in G0/G1 phaseand promoted cell apoptosis in SAOS2 and MG-63 cells. Bioinformatics analysis revealed that miR-125b-5p might be of complementary binding region with Circ_0086996, which was confirmed by dual-luciferase reporter assay. Moreover, Circ_0086996 could reverse the effect of miR-125b-5p, as knockdown of Circ_0086996 or application of miR-125b-5p both can inhibit cell proliferation, migration, invasion and promote cell apoptosis and cell cycle arrest. Our study discovers that Circ_0086996 acts as miR-125b-5p sponge to mediate the tumorigenicity, which could act as a potential biomarker for the osteosarcoma and provides a novel insight for the mechanism in osteosarcoma.

摘要

环状 RNA(CircRNAs)已被发现在肿瘤发生中起关键作用;然而,CircRNAs 在骨肉瘤中的作用有待进一步研究。在这项研究中,我们初步鉴定了骨肉瘤中上调的 CircRNAs 及其下游 microRNA,并研究了其潜在的调控机制。与相邻组织相比,hsa_circ_0086996(Circ_0086996)在肿瘤组织中上调。Circ_0086996 在骨肉瘤组织以及骨肉瘤细胞系 SAOS2 和 MG-63 中均显著过表达。Circ_0086996 敲低显著抑制细胞增殖、迁移和侵袭。Circ_0086996 敲低还诱导 SAOS2 和 MG-63 细胞周期停滞在 G0/G1 期,并促进细胞凋亡。生物信息学分析显示,miR-125b-5p 可能与 Circ_0086996 有互补结合区,这通过双荧光素酶报告基因实验得到证实。此外,Circ_0086996 可以逆转 miR-125b-5p 的作用,Circ_0086996 的敲低或 miR-125b-5p 的应用都可以抑制细胞增殖、迁移、侵袭,促进细胞凋亡和细胞周期停滞。我们的研究发现 Circ_0086996 作为 miR-125b-5p 的海绵来介导肿瘤发生,它可以作为骨肉瘤的潜在生物标志物,并为骨肉瘤的机制提供了新的见解。

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