Circ_LRP6 facilitates osteosarcoma progression via the miR-122-5p/miR-204-5p/HMGB1 axis

Environ Toxicol. 2023 Oct;38(10):2462-2475. doi: 10.1002/tox.23884. Epub 2023 Jul 14.

Abstract

Circ_LRP6 is participated in the occurrence and development of numerous tumors. Nevertheless, its roles and mechanism in osteosarcoma (OS) is unknown. This study aims to illustrate this point. With the use of qRT-PCR, the level of circ_LRP6, miR-122-5p, miR-204-5p and HMGB1 was identified. To observe cell proliferation, migration and invasion, we adopted CCK-8 and Transwell assays in the present study. Besides, to prove the existing interaction, bioinformatics analysis and dual luciferase reporting assays were employed. The influence of circ_LRP6 on osteosarcoma in vivo was evaluated by subcutaneous tumor formation model in nude mice. In osteosarcoma tissues, circ_LRP6 and HMGB1 are strongly denoted, whereas miR-122-5p and miR-204-5p are under-expressed. Circ_LRP6 knockdown could significantly hinder the proliferation, migration and invasion of osteosarcoma cells. Circ_LRP6 hindered the proliferation of osteosarcoma in vivo. Bioinformatics predicted that miR-122-5p and miR-204-5p functioned as direct targets of circ_LRP6, and HMGB1 were possible target genes of miR-122-5p and miR-204-5p. The findings indicated that the low level of miR-122-5p and miR-204-5p and the overexpression of HMGB1 could partially restore and reduce the inhibitory impact of circ_LRP6 on the proliferation, migration and invasion of osteosarcoma cells. Circ_LRP6 affects osteosarcoma progression via the miR-122-5p/miR-204-5p/HMGB1 axis, and is shown to be a molecular biomarker.

Keywords: HMGB1; circ_LRP6; miR-122-5p; miR-204-5p; osteosarcoma; proliferation.

MeSH terms

  • Animals
  • Bone Neoplasms* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • HMGB1 Protein* / genetics
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Osteosarcoma* / genetics

Substances

  • HMGB1 Protein
  • MicroRNAs
  • Mirn122 microRNA, mouse