Hox transcript antisense RNA knockdown inhibits osteosarcoma progression by regulating the phosphoinositide 3-kinase/AKT pathway through the microRNA miR-6888-3p/spleen tyrosine kinase axis

Abstract

ABSTRACT Long non-coding RNA HOX transcript antisense RNA (lncRNA HOTAIR) is thought to be a key regulator of the occurrence and development of osteosarcoma (OS). The expression of HOTAIR, microRNA miR-6888-3p, spleen tyrosine kinase (SYK), and phosphoinositide 3-kinase/AKT (PI3K/AKT) pathway-related proteins in OS was detected by quantitative reverse transcription-PCR (qRT-PCR) and western blotting. Changes in the proliferation and migration of OS cells were detected by Cell Counting Kit-8 (CCK-8) and transwell assays after the knockdown of HOTAIR, miR-6888-3p, or SYK. Luciferase assays, RNA immunoprecipitation (RIP), and RNA pull-down assays were used to detect the relationship between miR-6888-3p and HOTAIR or SYK. We found that HOTAIR and SYK were highly expressed in OS, whereas miR-6888-3p expression was low. In addition, downregulation of HOTAIR or SYK significantly inhibited the growth and migration of OS cells and the PI3K/AKT pathway, both in vitro and in vivo. Additionally, downregulation of miR-6888-3p promoted the proliferation and migration of OS cells and activated the PI3K/AKT pathway. Mechanistically, these results suggest that the HOTAIR sponge, miR-6888-3p, regulates SYK expression. To summarize, HOTAIR regulates SYK by acting on miR-6888-3p, thereby promoting the proliferation and migration of OS cells.