circ-LRP6 contributes to osteosarcoma progression by regulating the miR-141-3p/HDAC4/HMGB1 axis

Abstract

Circular RNA-lipoprotein receptor 6 (circ-LRP6) serves a role in promoting the tumorigenesis of retinoblastoma, esophageal squamous cell cancer and oral squamous cell carcinoma; however, whether circ-LRP6 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 circ-LRP6 in OS. The expression levels of circ-LRP6, microRNA (miR)-141-3p, histone deacetylase 4 (HDAC4) and high mobility group protein 1 (HMGB1) were evaluated by reverse transcriptionquantitative PCR in OS tissues and cell lines. Cell Counting Kit-8, 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 dual-luciferase reporter assays were used to predict and analyze the interactions between circ-LRP6 and miR-141-3p, miR-141-3p and HDAC4, as well as between miR-141-3p and HMGB1. Additionally, RNA immunoprecipitation was performed to verify the association between circ-LRP6 and miR-141-3p. The results confirmed that circ-LRP6 was highly expressed in OS tissues and cell lines. In addition, circ-LRP6 negatively regulated the expression of miR-141-3p and, in turn, miR-141-3p negatively regulated HDAC4 and HMGB1 expression. Functional assays revealed that circ-LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells, whereas the inhibition of miR-141-3p or the overexpression of either HDAC4 or HMGB1 partly reversed the inhibitory effect of circ-LRP6 knockdown. In summary, the present study determined that circ-LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells by regulating the miR-141-3p/HDAC4/HMGB1 axis.