LncRNA LINC00210 regulated radiosensitivity of osteosarcoma cells via miR-342-3p/GFRA1 axis

J Clin Lab Anal. 2020 Dec;34(12):e23540. doi: 10.1002/jcla.23540. Epub 2020 Aug 25.

Abstract

Background: Radiotherapy is an effective strategy for preventing cancer metastasis, including osteosarcoma. However, cancer radioresistance limits the efficiency of radiotherapy. Therefore, it is essential to investigate the mechanism of osteosarcoma radioresistance.

Methods: The osteosarcoma tissues and adjacent healthy tissues were collected from 53 osteosarcoma patients. The expression of LINC00210, miR-342-3p, and GFRA1 mRNA were determined using qRT-PCR. Cell viability, cell apoptosis, and cell surviving fraction were determined by MTT assay, flow cytometry, and colony formation assay, respectively. Western blot was performed to detect the protein levels. Luciferase assay was conducted to verify the relationship between LINC00210, miR-342-3p, and GFRA1.

Results: LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma tissues and cells. The expression of LINC00210 in osteosarcoma was negatively related to miR-342-3p expression and positively associated with GFRA1. Besides, there was a negative correlation between LINC00210 and GFRA1 expression in osteosarcoma. Also, LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma cells exposed to 4 Gy irradiation treatment. Furthermore, either LINC00210 knockdown or miR-342-3p overexpression enhanced the radiosensitivity of osteosarcoma cells. Moreover, LINC00210 increased GFRA1 expression via sponging miR-342-3p. Additionally, LINC00210 knockdown improved the radiosensitivity of osteosarcoma cells by regulating GFRA1 expression via sponging miR-342-3p.

Conclusion: LINC00210 modulated the radiosensitivity of osteosarcoma cells via the miR-342-3p/GFRA1 axis, making LINC00210 a novel target for improving radiotherapy efficiency in osteosarcoma.

Keywords: GFRA1; LINC00210; miR-342-3p; osteosarcoma; radiosensitivity.

MeSH terms

  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / metabolism
  • Bone Neoplasms* / pathology
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • Osteosarcoma* / pathology
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Radiation Tolerance / genetics*

Substances

  • GFRA1 protein, human
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • MIRN342 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding