LINC01255 combined with BMI1 to regulate human mesenchymal stromal senescence and acute myeloid leukemia cell proliferation through repressing transcription of MCP-1

Clin Transl Oncol. 2021 Jun;23(6):1105-1116. doi: 10.1007/s12094-020-02505-5. Epub 2021 Jan 6.

Abstract

Background: Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular biology processes, for example, participate in chromatin remodeling, imprinting, splicing, transcriptional regulation and translation. Dysregulation of lncRNA expression is act as a feature of various diseases and cancers, including hematopoietic malignancies. However, the clinical relevance of myelodysplastic syndrome (MDS) and acute myeloid leukemia preceded by MDS (MDS-AML) requires further research. Recently, lncRNAs have been demonstrated, which play an important role in hematopoiesis, thus, to further finding more functional lncRNA seemed particularly important.

Methods: Western blotting, real-time PCR, RNA-pulldown, RIP (RNA immunoprecipitation), Chromatin immunoprecipitation (ChIP), cellular compartments extraction assays, SA-β-gal staining, lentivirus transfection, cell viability assay and cell proliferation assays were used to examine the relationship between lncRNA LINC01255 and its regulation of p53-p21 pathway in human mesenchymal stromal and acute myeloid leukemia cells.

Results: LncRNA LINC01255 is highly expressed in bone marrow cells of AML patients, CD34+ cells of MDS-AML patients and AML cell lines and the higher expression of LINC01255 is associated with poor survival rate of AML patients. LINC01255 can interact with BMI1 and repress the transcription of MCP-1 to active p53-p21 pathway, thus inhibiting the senescence of human mesenchymal stromal and proliferation of acute myeloid leukemia cell.

Conclusions: We discovered a novel functional lncRNA LINC01255, which can regulate the senescence of human mesenchymal stromal and the proliferation of acute myeloid leukemia cell through inhibiting the transcription of MCP-1.

Keywords: AML; BMI1; MCP-1; MDS; lncRNA LINC01255.

MeSH terms

  • Cell Proliferation*
  • Cellular Senescence / genetics*
  • Chemokine CCL2 / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / pathology*
  • Mesenchymal Stem Cells / pathology*
  • Polycomb Repressive Complex 1 / physiology*
  • RNA, Long Noncoding / physiology*
  • Transcription, Genetic*
  • Tumor Cells, Cultured

Substances

  • BMI1 protein, human
  • CCL2 protein, human
  • Chemokine CCL2
  • RNA, Long Noncoding
  • Polycomb Repressive Complex 1