环状MMP9的上调通过靶向miR-1265/CHI3L1轴促进骨肉瘤进展。
Upregulation Of circMMP9 Promotes Osteosarcoma Progression Via Targeting miR-1265/CHI3L1 Axis.
作者信息
Pan Guangjie, Hu Ting, Chen Xuewu, Zhang Chao
机构信息
Department of Orthopedics, Wenzhou Central Hospital, Wenzhou 325000, People's Republic of China.
Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China.
出版信息
Cancer Manag Res. 2019 Oct 29;11:9225-9231. doi: 10.2147/CMAR.S226264. eCollection 2019.
BACKGROUND
Osteosarcoma (OS) is a very aggressive cancer. Nevertheless, how circular RNA (circRNA) contributes to OS progression remains unclear. Here, we aimed to research the functions of circMMP9 in OS progression.
METHODS
Gene expression was determined via qRT-PCR. siRNA was used to knock down circMMP9. Proliferation was analyzed using CCK8 and colony formation assays. Migration and invasion were measured using Transwell assay.
RESULTS
circMMP9 was overexpressed in cancer tissues. Overexpressed circMMP9 was correlated with advanced tumor stage and predicted poor prognosis. circMMP9 knockdown exhibited a tumor-suppressive phenotype via suppressing proliferation, migration and invasion. Besides, decreased circMMP9 level promoted OS cellular apoptosis. Mechanistically, circMMP9 was shown to be located in the cytoplasm and sponge miR-1265. Furthermore, miR-1265 directly targeted CHI3L1. CHI3L1 levels were modulated by circMMP9/miR-1265 axis. Rescue experiments indicated that circMMP9 contributes to OS development through the miR-1265/CHI3L1 pathway.
CONCLUSION
Our findings provide a novel insight about how circRNA regulates OS progression.
背景
骨肉瘤（OS）是一种侵袭性很强的癌症。然而，环状RNA（circRNA）如何促进骨肉瘤进展仍不清楚。在此，我们旨在研究circMMP9在骨肉瘤进展中的作用。
方法
通过qRT-PCR测定基因表达。使用小干扰RNA（siRNA）敲低circMMP9。采用CCK8和集落形成实验分析细胞增殖情况。使用Transwell实验检测细胞迁移和侵袭能力。
结果
circMMP9在癌组织中高表达。circMMP9高表达与肿瘤晚期相关，并预示预后不良。敲低circMMP9通过抑制增殖、迁移和侵袭表现出肿瘤抑制表型。此外，circMMP9水平降低促进骨肉瘤细胞凋亡。机制上，circMMP9定位于细胞质并可吸附miR-1265。此外，miR-1265直接靶向CHI3L1。CHI3L1水平受circMMP9/miR-1265轴调控。挽救实验表明，circMMP9通过miR-1265/CHI3L1途径促进骨肉瘤发展。
结论
我们的研究结果为circRNA如何调节骨肉瘤进展提供了新的见解。
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