Knockdown of lncRNA LINC00662 suppresses malignant behaviour of osteosarcoma cells via competition with miR-30b-3p to regulate ELK1 expression

Journal of Orthopaedic Surgery and Research

Zhenchao Gao¹  Shengli Xia²  Pan Cai²  Minghui Wang²  Xiuhui Wang²  Zhengfeng Xu²  Bin Wang² 

[1]Department of Orthopedics, Shanghai Public Health Clinical Center, No. 2901, Caolang Road, Jinshan District, 201508, Shanghai City, China

[2]Department of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, No. 1500, Zhouyuan Road, Pudong New District, 201318, Shanghai City, China

关键词: Osteosarcoma;    microRNAs;    Long non-coding RNA LINC00662;    miR-30b-3p;    ELK1;   

DOI  :  10.1186/s13018-022-02964-2

来源: Springer

【 摘 要 】

PurposeOsteosarcoma is a type of bone malignancy that mainly occurred in teenagers. This investigation is aimed to clarify the effect of long non-coding RNA (lncRNA) LINC00662 on the proliferation, migration, and invasion in osteosarcoma and explore the underlying action mechanisms.MethodsThe mRNA expression of LINC00662 was determined by real-time quantitative polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and transwell assays, respectively. A dual-luciferase reporter assay was used to validate the target relationships Between microRNA (miR)-30b-3p and LINC00662/ ETS domain-containing protein 1 (ELK1). Western blotting was performed to determine the protein expression of ELK1. Xenograft model was established to evaluate the effects of LINC00662 silencing on tumor growth in vivo.ResultsLncRNA LINC00662 and ELK1 were significantly increased, while miR-30b-3p was reduced in osteosarcoma tissues. The results of functional experiments indicated that transfection of small hairpin (sh)-LINC00662 and miR-30b-3p mimics repressed the migration, invasion, and proliferation of osteosarcoma cells. LncRNA LINC00662 also appeared to sponge miR-30b-3p in order to affect the expression of ELK1. Simultaneously, there were weak negative correlations between the expression of miR-30b-3p and LINC00662/ELK1 in osteosarcoma tissues. Rescue experiments suggested that ELK1 overexpression and downregulation of miR-30b-3p reversed the suppressive effects of sh-LINC00662 on the cell migration, invasion, and proliferation in osteosarcoma.ConclusionsThe current study indicated that knockdown of LINC00662 repressed cell migration, invasion, and proliferation through sponging miR-30b-3p to regulate the expression of ELK1 in osteosarcoma. These results may uncover a promising target for the treatment of osteosarcoma.

【 授权许可】

CC BY