circ­LRP6 contributes to osteosarcoma progression by regulating the miR­141­3p/HDAC4/HMGB1 axis.

Circular RNA­lipoprotein receptor 6 (circ­LRP6) serves a role in promoting the tumorigenesis of retinoblastoma, esophageal squamous cell cancer and oral squamous cell carcinoma; however, whether circ­LRP6 demonstrates the same effect in osteosarcoma (OS) is yet to be fully elucidated. The present study aimed to analyze the expression, role and potential molecular mechanism of circ­LRP6 in OS. The expression levels of circ­LRP6, microRNA (miR)­141­3p, histone deacetylase 4 (HDAC4) and high mobility group protein 1 (HMGB1) were evaluated by reverse transcription-quantitative PCR in OS tissues and cell lines. Cell Counting Kit­8, Transwell and Matrigel assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Western blotting was also performed to determine HDAC4 and HMGB1 protein expression levels. Bioinformatics and dual­luciferase reporter assays were used to predict and analyze the interactions between circ­LRP6 and miR­141­3p, miR­141­3p and HDAC4, as well as between miR­141­3p and HMGB1. Additionally, RNA immunoprecipitation was performed to verify the association between circ­LRP6 and miR­141­3p. The results confirmed that circ­LRP6 was highly expressed in OS tissues and cell lines. In addition, circ­LRP6 negatively regulated the expression of miR­141­3p and, in turn, miR­141­3p negatively regulated HDAC4 and HMGB1 expression. Functional assays revealed that circ­LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells, whereas the inhibition of miR­141­3p or the overexpression of either HDAC4 or HMGB1 partly reversed the inhibitory effect of circ­LRP6 knockdown. In summary, the present study determined that circ­LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells by regulating the miR­141­3p/HDAC4/HMGB1 axis.