Long noncoding RNA RHPN1-AS1 exerts pro-oncogenic actions in osteosarcoma by functioning as a molecular sponge of miR-506 to positively regulate SNAI2 expression

摘要

The long noncoding RNA, RHPN1 antisense RNA 1 (RHPN1-AS1), performs important regulatory actions in the progression of many human cancers. In this study, we aimed to analyzeRHPN1-AS1expression in osteosarcoma (OS) and to assess the influence ofRHPN1-AS1knockdown on the malignant behavior of OS cells. The molecular mechanisms by whichRHPN1-AS1affects the oncogenicity of OS were explored too. The expression ofRHPN1-AS1in OS was measured by RT-qPCR. The effects of theRHPN1-AS1silencing in OS cells were studied both in vitro (in a Cell Counting Kit-8 assay, apoptosis analysis, and Transwell migration and invasion assays) and in vivo (by means of tumor xenografts in nude mice). Herein,RHPN1-AS1expression was found to be significantly upregulated in OS tissues and cell lines. The elevated expression ofRHPN1-AS1closely correlated with the tumor size, TNM stage, distal metastasis and shorter overall survival in patients with OS. The depletion ofRHPN1-AS1restrained OS cell proliferation, migration, and invasion, and exerted proapoptotic effects in vitro. Furthermore, the knockdown ofRHPN1-AS1effectively reduced the tumor growth of OS cells in vivo. As for the mechanism,RHPN1-AS1increased snail family zinc finger 2 (SNAI2 also known as SNAIL2) expression by acting as a competing endogenous RNA of miR-506. Notably, increasing the amount of miR-506 partially reversed the effects of theRHPN1-AS1downregulation on OS cells. In conclusion,RHPN1-AS1contributes to the malignancy of OS cells in vitro and in vivo, largely via upregulation of the miR-506-SNAI2 axis output.