MiRNA-301b-3p induces proliferation and inhibits apoptosis in AML cells by targeting FOXF2 and regulating Wnt/β-catenin axis

  • Mol Cell Probes. 2022 Jun:63:101805. doi: 10.1016/j.mcp.2022.101805.
Yang Lu  1 ,  Liang Zhong  2 ,  Xu Luo  1 ,  Chen Liu  2 ,  Wenran Dan  1 ,  Xuan Chu  1 ,  Peng Wan  1 ,  Zhonghui Zhang  1 ,  Xiao Wang  1 ,  Zhenyan Liu  1 ,  Beizhong Liu  3
Affiliations
  • 1. Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China.
  • 2. Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
  • 3. Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].
PMID: 35259424 DOI: 10.1016/j.mcp.2022.101805
Abstract

Background: MiRNA-301b-3p functions as an oncomiRNA or tumor suppressor, and has been reported in various Cancer types, including pancreatic, colorectal, oral, hepatocellular and lung cancers. Although the expression of miRNA-301b-3p is upregulated in Acute Myeloid Leukemia (AML), its biological function and precise mechanisms remain unclarified. This study explores the roles of miRNA-301b-3p in AML, with the aim of ascertaining its regulatory action on Wnt/β-catenin axis by targeting Forkhead box F2 (FOXF2).

Methods: The expression levels of miRNA-301b-3p and FOXF2 were measured by quantitative Real-Time PCR. The effects of miRNA-301b-3p knockdown and overexpression on cell proliferation were evaluated by CCK8 and cell counting assays, while cell Apoptosis was analyzed by flow cytometry. The expression levels of apoptosis-related proteins, including FOXF2, and other targets in Wnt/β-catenin axis were determined by immunoblotting. Possible interaction between miRNA-301-3p and FOXF2 in AML cells was examined by luciferase reporter assays.

Results: MiRNA-301b-3p was dramatically upregulated in AML cells, and showed a negative correlation with FOXF2 expression. Downregulation of miRNA-301b-3p suppressed proliferation and promoted Apoptosis in AML cells. MiRNA-301b targeted FOXF2 to regulate Wnt/β-catenin axis. In the rescue experiments, FOXF2 overexpression partly reversed the effect of miRNA-301b-3p mimic in AML cells.

Conclusion: The current findings demonstrate that miRNA-301b-3p targets FOXF2 to induce proliferation and inhibit Apoptosis in AML cells via regulation of Wnt/β-catenin axis.

Keywords
Acute myeloid leukemia; Apoptosis; Forkhead box F2; Proliferation; Wnt/β-catenin pathway; miRNA-301b-3p.
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