miR-148a-3p suppresses the progression of acute myeloid leukemia via targeting cyclin-dependent kinase 6 (CDK6)

Bioengineered. 2021 Dec;12(1):4508-4519. doi: 10.1080/21655979.2021.1956400.

Abstract

To study the regulation of miR-148a-3p on CDK6 and its mechanism in the progress of acute myeloid leukemia (AML), differential miRNAs were analyzed by bioinformatics, and the miR-148a-3p levels in AML cell lines were detected. Results showed that miR-148a-3p played a crucial role in AML, and the level was lower in AML cells, especially in J111 and KG-1a cells. In J111 and KG-1a cells, the up-regulation of miR-148a-3p mimics blocked the cell growth by arresting cell cycle at G2/M and enhancing cell apoptosis. Transwell and EMT markers detection indicated that miR-148a-3p reduced the cell migration and invasion. Afterward, through bioinformatics analysis, it showed that the CDK6 is one of the direct target genes of miR-148a-3p. DLR assay confirmed the target regulation. CDK6 overexpression reversed the effects of miR-148a-3p on AML cells. Collectively, miR-148a-3p inhibited the process of AML cells through disturbing the CDK-6 expression, implying that the trageting miR-148a-3p might be regarded as effective therapy of AML.

Keywords: CDK6; acute myeloid leukemia; invasion; migration; mir-148a-3p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase 6* / genetics
  • Cyclin-Dependent Kinase 6* / metabolism
  • Disease Progression
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • MIRN148 microRNA, human
  • MicroRNAs
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6

Grants and funding

This work was supported in part by the National Natural Science Foundation of China (grant no. 81600129), Natural Science Foundation of Zhejiang Province (grant no. LY21H080001), The Science and Technology Project of Hangzhou (grant no. 2016Z01, 2017A11) and Clinical Research Fund of Zhejiang Medical Association (grant no. 2018ZYC-A31).