环状 RNA IARS 通过从 RAB14 海绵化 miR-188-5p 调节骨肉瘤的进展和铁变态反应。

IF 2 4区 医学 Q3 ONCOLOGY Neoplasma Pub Date : 2024-06-01 DOI:10.4149/neo_2024_240312N111
Yafei Li, Yan Zhang, Xiaohong Lu, Ruie Li, Jiayu Peng, Yangbo Xu
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引用次数: 0

摘要

骨肉瘤(Osteosarcoma,OS)是儿童和青少年中常见的原发性骨肿瘤。环状 RNA(circRNA)-IARS 是多种人类肿瘤的致癌基因。然而,circ-IARS在OS中的功能尚不清楚。本研究旨在阐明circ-IARS在OS中的作用和机制。该研究发现,circ-IARS在OS组织和细胞中的表达升高,circ-IARS的表达与临床分期和远处转移密切相关。此外,高circ-IARS水平的OS患者总生存率降低。同时,沉默circ-IARS会减弱OS细胞的增殖和侵袭,但会增强细胞的铁变态反应。从机理上讲,circ-IARS靶向miR-188-5p调节OS细胞中RAB14的表达。此外,circ-IARS敲除抑制了OS细胞的增殖和侵袭,并诱导了铁凋亡,而与抗miR-188-5p或pcDNA-RAB14联合转染则可消除这些影响。同时,干扰circ-IARS可减少OS细胞的增殖,降低RAB14(RAS癌基因家族成员)、GPX4和xCT(重要的铁变态调节因子)在体内的表达。总之,circ-IARS通过miR-188-5p/RAB14促进了OS的进展。
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Circular RNA IARS modulates the progression and ferroptosis of osteosarcoma via sponging miR-188-5p from RAB14.

Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14.

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来源期刊
Neoplasma
Neoplasma 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
238
审稿时长
3 months
期刊介绍: The journal Neoplasma publishes articles on experimental and clinical oncology and cancer epidemiology.
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