Circular RNA hsa_circ_0001564 regulates osteosarcoma proliferation and apoptosis by acting miRNA sponge

Biochem Biophys Res Commun. 2018 Jan 15;495(3):2369-2375. doi: 10.1016/j.bbrc.2017.12.050. Epub 2017 Dec 9.

Abstract

Circular RNAs (circRNAs) is a novel type of non-coding RNAs generated from back splicing, which has been verified to mediate multiple tumorigenesis. However, the role of circRNA in osteosarcoma is still unclear. In the present study, we preliminarily screened the circRNAs expression profiles in osteosarcoma and investigated the potential regulation mechanism. The circRNAs expression profiles in osteosarcoma were screened using circRNA microarray analysis, and results showed that there were 1152 circRNAs up-regulated and 915 circRNAs down-regulated in tumor tissue compared to adjacent tissue. Hsa_circ_0001564, located at 5q35.3 and its associated-gene symbol is CANX, was one of the significantly overexpressed circRNAs in osteosarcoma tissue, as well as in osteosarcoma cell lines. In functional experiments, hsa_circ_001564 knockdown significantly suppressed the proliferation activity, induced cell cycle arrest in G0/G1 phase, and promoted apoptosis in HOS and MG-63 cells. Subsequently, we explored the probable mechanism of hsa_circ_001564, and fortunately, bioinformatics analysis revealed that miR-29c-3p contained the complementary binding region with hsa_circ_0001564, which was confirmed by dual-luciferase reporter assay. Moreover, rescue experiments illustrated that miR-29c-3p could reverse the oncogenesis effect of hsa_circ_001564. Our study discovers that hsa_circ_0001564 acts as miR-29c-3p sponge to mediate the tumorigenicity, which could act as a potential biomarker for the osteosarcoma and provide a novel insight for competing endogenous RNAs (ceRNAs) mechanism in osteosarcoma.

Keywords: Circular RNA; Osteosarcoma; ceRNA; miR-29c-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Carcinogenesis / genetics
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • RNA / genetics*
  • RNA, Circular
  • Tumor Cells, Cultured

Substances

  • MicroRNAs
  • RNA, Circular
  • RNA