Aging
Navigate
Submit an Article
Research Paper|Volume 13, Issue 23|pp 25484—25495

Hsa_circ_0008259 modulates miR-21-5p and PDCD4 expression to restrain osteosarcoma progression

Kai Guan1, Shizhang Liu2, Keke Duan2, Xiaoxia Zhang2, Huitong Liu2, Bingqiang Xu2, Xi Wang2, Xin Jin1
  • 1The Second Department of Orthopaedics, The First People's Hospital of Xianyang, Xianyang 712000, Shaanxi Province, China
  • 2Department of Orthopedics, Shaanxi Provincial People’s Hospital, The Third Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710068, Shaanxi Province, China
Received: March 13, 2021Accepted: November 11, 2021Published: December 14, 2021
https://doi.org/10.18632/aging.203769

Copyright: © 2021 Guan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Osteosarcoma (OS) is one of the most common primary bone tumors in children and adolescents. However, the molecular mechanism of OS tumorigenesis is still little known. Circular RNA (circRNA) is a key player in the progression of many cancers. This study is performed to decipher the role and mechanism of circ_0008259 in the progression of OS.

Methods: A differentially expressed circRNA, circ_0008259, was screened out by analyzing the expression profile of circRNA in OS tissue. Circ_0008259, miR-21-5p and programmable cell death 4 (PDCD4) mRNA expression levels in OS tissues and cells were detected by qRT-PCR. Cell viability, metastatic potential and apoptosis were evaluated by cell counting kit-8 assay, Transwell and flow cytometry. The targeting relationship between circ_0008259 and miR-21-5p, and miR-21-5p and PDCD4 mRNA was analyzed and probed by bioinformatics analysis and dual-luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA-pull down assay. The regulatory effects of circ_0008259 and miR-21-5p on PDCD4 protein expression in OS cells were detected by Western blot assay.

Results: Circ_0008259 expression and PDCD4 expression were down-regulated and miR-21-5p expression was elevated in the OS tissues and cells. Functional experiments showed that circ_0008259 overexpression significantly inhibited the proliferation and metastatic potential of OS cells and promoted the apoptosis. Besides, PDCD4 was validated as the target gene of miR-21-5p, and circ_0008259 could competitively bind to miR-21-5p, thus up-regulating PDCD4 expression in OS cells.

Conclusions: Circ_0008259 suppresses OS progression via regulating miR-21-5p/PDCD4 axis.