Lu Zhaoan, Wang Chuanwen, Lv Xiaolong, Dai Wen
Department of Orthopedics, the First People's Hospital of Shangqiu City, Shangqiu 476100, Henan, China.
J Bone Oncol. 2021 Apr 22;28:100360. doi: 10.1016/j.jbo.2021.100360. eCollection 2021 Jun.
Circular RNAs (circRNAs) are a class of endogenous RNAs that are involved in osteosarcoma progression. Hsa_circ_0010220 (circ_0010220) is a circRNA generated by gene Rho Guanine Nucleotide Exchange Factor 10 Like (ARHGEF10L) and is upregulated in osteosarcoma, but its functional role in osteosarcoma is limited studied. This study aimed to illustrate the regulatory mechanism underlying circ_0010220 in osteosarcoma.
51 paired tumor and normal tissues were obtained from osteosarcoma patients. circ_0010220, microRNA (miR)-198 and Syntaxin 6 (STX6) abundances were examined by quantitative reverse transcription polymerase chain reaction and western blot. Cell proliferation, cell cycle, apoptosis, migration and invasion were analyzed via Cell Counting Kits-8 (CCK-8), colony formation, flow cytometry and transwell analyses. Target relationship was verified via dual-luciferase reporter analysis, RNA immunoprecipitation and pull-down. The function was analyzed using a xenograft model.
Circ_0010220 was elevated in osteosarcoma tissues and cells, and was related to the lower survival rate of osteosarcoma patients. Circ_0010220 knockdown inhibited cell proliferation, migration and invasion, but induced cell cycle arrest and apoptosis . Besides, circ_0010220 silence curbed the growth of xenograft osteosarcoma tumors . Mechanistic research revealed that miR-198 is a target of circ_0010220, and directly targets STX6. Moreover, circ_0010220 upregulated the expression of STX6 by sponging miR-198 to regulate cell proliferation, migration, invasion, cell cycle, and apoptosis.
Circ_0010220 contributes to osteosarcoma progression through mediating miR-198/STX6 axis, which might be a novel therapeutic target for osteosarcoma therapy.
环状RNA（circRNAs）是一类参与骨肉瘤进展的内源性RNA。Hsa_circ_0010220（circ_0010220）是一种由基因Rho鸟嘌呤核苷酸交换因子10样蛋白（ARHGEF10L）产生的环状RNA，在骨肉瘤中上调，但其在骨肉瘤中的功能作用研究有限。本研究旨在阐明circ_0010220在骨肉瘤中的调控机制。
从骨肉瘤患者中获取51对肿瘤组织和正常组织。通过定量逆转录聚合酶链反应和蛋白质免疫印迹法检测circ_0010220、微小RNA（miR）-198和Syntaxin 6（STX6）的丰度。通过细胞计数试剂盒-8（CCK-8）、集落形成、流式细胞术和Transwell分析来分析细胞增殖、细胞周期、凋亡、迁移和侵袭。通过双荧光素酶报告基因分析、RNA免疫沉淀和下拉实验验证靶标关系。使用异种移植模型分析其功能。
Circ_0010220在骨肉瘤组织和细胞中升高，并且与骨肉瘤患者较低的生存率相关。Circ_0010220敲低抑制细胞增殖、迁移和侵袭，但诱导细胞周期停滞和凋亡。此外，circ_0010220沉默抑制了异种移植骨肉瘤肿瘤的生长。机制研究表明，miR-198是circ_0010220的靶标，并且直接靶向STX6。此外，circ_0010220通过海绵吸附miR-198上调STX6的表达，从而调节细胞增殖、迁移、侵袭、细胞周期和凋亡。
Circ_0010220通过介导miR-198/STX6轴促进骨肉瘤进展，这可能是骨肉瘤治疗的一个新的治疗靶点。
