LncRNA DLX6-AS1 promotes tumor proliferation and metastasis in osteosarcoma through modulating miR-641/HOXA9 signaling pathway.

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor. Recently, increasing evidence has shown that the long noncoding RNA (lncRNA) DLX6-AS1 (distal-less homeobox 6 antisense 1) plays significant roles in various types of cancers. However, the functions and underlying mechanisms of DLX6-AS1 have not been explored in OS yet. In this study, we assessed the expression of DLX6-AS1 in OS tissues and cell lines and explored the underlying molecular mechanisms. DLX6-AS1 was found to be significantly upregulated in OS tissues and OS cell lines. High expression of DLX6-AS1 was significantly correlated with advanced TNM stage, high tumor grade, and distant metastasis of patients with OS. Knockdown of DLX6-AS1 suppressed OS cell proliferation, invasion, and migration, and induced cell apoptosis. Knockdown of DLX6-AS1 also suppressed in vivo tumor growth. Bioinformatics and luciferase assay analysis showed that DLX6-AS1 functioned as a competing endogenous RNA (ceRNA) to negatively regulate miR-641 expression. Furthermore, miR-641 was found to target the 3' untranslated region of homeobox protein Hox-A9 (HOXA9) and suppressed the expression of HOXA9. Mechanistic studies showed that DLX6-AS1 regulated OS cell proliferation, invasion, and migration via regulating HOXA9 by acting as a ceRNA for miR-641. Our results suggested that DLX6-AS1 functions as a ceRNA by targeting miR-641/HOXA9 signal pathway to suppress OS cell proliferation and metastasis. Our study may provide novel insights into understanding pathogenesis and development of OS.