LncRNA SCIRT is Downregulated in Acute Myeloid Leukemia and Sponges miR-21 in Cytoplasm to Increase Chemosensitivity to Doxorubicin

Crit Rev Eukaryot Gene Expr. 2022;32(3):61-69. doi: 10.1615/CritRevEukaryotGeneExpr.2021039618.

Abstract

Background: This study aimed to explore the role of SCIRT in acute myeloid leukemia (AML) and its interaction with miR-21.

Methods: This study included 66 AML patients who were diagnosed with AML and received doxorubicin (Dox) treatment. Bone marrow was isolated from all patients before and after treatment to prepare BM mononuclear cells (BMMNCs). BMMNCs from another 60 healthy controls were also collected. The expression of SCIRT and miR-21 were analyzed with RT-qPCR. Subcellular location of SCIRT was analyzed with cellular fractionation assay. RNA pull-down assay was performed to analyze the interaction between SCIRT and miR-21. The roles of SCIRT and miR-21 in regulating the expression of each other were explored with overexpression assay. The role of SCIRT and miR-21 in Dox-induced AML cell apoptosis was analyzed with cell apoptosis assay.

Results: SCIRT was downregulated in AML and further downregulated in AML patients who developed drug resistance (DR) after treatment. In contrast, miR-21 was upregulated in AML and further upregulated in AML patients with DR. SCIRT was detected in both nuclear and cytoplasm and it directly interacted with miR-21. SCIRT and miR-21 did not affect the expression of each other. In contrast, SCIRT suppressed the inhibitory role of miR-21 in the apoptosis of AML cells induced by Dox.

Conclusion: In conclusion, SCIRT was downregulated in AML and it sponged miR-21 in cytoplasm to increase the chemosensitivity to Dox.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cytoplasm
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Doxorubicin