Circ_0081001 down-regulates miR-494-3p to enhance BACH1 expression and promotes osteosarcoma progression

Aging (Albany NY). 2021 Jun 30;13(13):17274-17284. doi: 10.18632/aging.203207. Epub 2021 Jun 30.

Abstract

The study was aimed at deciphering the function and mechanism of circ_0081001 in osteosarcoma (OS). In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for quantifying circ_0081001, miR-494-3p, and BTB domain and CNC homolog 1 (BACH1) mRNA expressions in OS tissues and cells. Cell counting kit-8 (CCK-8) assay, together with 5-Ethynyl-2'-deoxyuridine (EdU) assay, was performed for evaluating cell proliferation; the alterations in apoptosis were analyzed utilizing flow cytometry; Transwell assay was conducted for examining cell migration and invasion; moreover, Western blot was utilized for the quantification of BACH1 protein expression; bioinformatics, dual-luciferase reporter gene, and RNA-binding protein immunoprecipitation assays were executed for validating the binding relationships between circ_0081001 and miR-494-3p, and between miR-494-3p and BACH1. As shown, circ_0081001, whose expression was elevated in OS tissues, had a negative association with miR-494-3p expression and a positive correlation with BACH1 expression. After circ_0081001 was overexpressed, the proliferation, migration, and invasion of OS cells were boosted but the apoptosis was reduced, whereas miR-494-3p exhibited opposite effects. The binding sites between circ_0081001 and miR-494-3p, and between miR-494-3p and the 3'UTR of BACH1 were experimentally verified. In conclusion, circ_0081001/miR-494-3p/BACH1 axis promoted the malignant biological behaviors of OS cells.

Keywords: BACH1; circ_0081001; miR-494; osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adolescent
  • Adult
  • Aged
  • Apoptosis
  • Basic-Leucine Zipper Transcription Factors / biosynthesis
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Bone Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Computational Biology
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Osteosarcoma / genetics*
  • Prognosis
  • Young Adult

Substances

  • 3' Untranslated Regions
  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • MIRN494 microRNA, human
  • MicroRNAs