Circ-LAMP1 promotes T-cell lymphoblastic lymphoma progression via acting as a ceRNA for miR-615-5p to regulate DDR2 expression

Gene. 2019 Jun 15:701:146-151. doi: 10.1016/j.gene.2019.03.052. Epub 2019 Mar 25.

Abstract

Circular RNAs (circRNAs) act as pivotal functions in tumor progression. Nevertheless, the functions and mechanism of circRNAs in T-cell lymphoblastic lymphoma (T-LBL) remain unclear. In this work, we first screened the differentially expressed circRNAs between T-LBL tissues and normal infantile thymus and circ-LAMP1 was identified the highest expressed circRNA in cancerous tissues. qRT-PCR further verified its upregulation in T-LBL tissues and cell lines. Cell counting kit-8 (CCK-8) experiment proved the cell proliferation-promoting role of circ-LAMP1. This effect is partially dependent on its inhibition on cell apoptosis proved by flow cytometric assay. Dual-luciferase reporter system further identified that miR-615-5p could be sponged by circ-LAMP1 and discoidin domain receptor tyrosine kinase 2 (DDR2) 3'-UTR is the direct target of miR-615-5p. Rescue assays demonstrated that the biological function of circ-LAMP1 is partly attributed to the modulation of miR-615-5p/DDR2 signaling. In summary, these findings documented that circ-LAMP1 might be an oncogene in T-LBL, which might be useful in developing promising therapies for T-LBL.

Keywords: Circ-LAMP1; Circular RNA; Discoidin domain receptor tyrosine kinase 2; T-cell lymphoblastic lymphoma; miR-615-5p.

MeSH terms

  • 3' Untranslated Regions
  • Discoidin Domain Receptor 2* / biosynthesis
  • Discoidin Domain Receptor 2* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Jurkat Cells
  • Lymphoma, T-Cell* / genetics
  • Lymphoma, T-Cell* / metabolism
  • Lymphoma, T-Cell* / pathology
  • Lysosomal Membrane Proteins* / genetics
  • Lysosomal Membrane Proteins* / metabolism
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Proteins* / biosynthesis
  • Neoplasm Proteins* / genetics
  • RNA, Neoplasm* / genetics
  • RNA, Neoplasm* / metabolism

Substances

  • 3' Untranslated Regions
  • Lamp1 protein, rat
  • Lysosomal Membrane Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Ddr2 protein, rat
  • Discoidin Domain Receptor 2