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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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MicroRNA-181a Inhibits Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Progression by Repressing CARD11

Danxia Zhu1, Cheng Fang1, Wenting He1

  • 1Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Journal of Oncology
|October 31, 2019
PubMed

Insights

MicroRNA-181a (miR-181a) suppresses diffuse large B-cell lymphoma (DLBCL) by targeting CARD11. Lower miR-181a levels in ABC-like DLBCL correlate with higher CARD11, promoting tumor growth and invasiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous non-Hodgkin lymphoma.
  • Activated B-cell-like (ABC) DLBCL is associated with a poorer prognosis compared to germinal center B-cell-like (GCB) DLBCL.
  • MicroRNAs (miRNAs) play crucial roles in cancer development and progression.

Purpose of the Study:

  • To investigate the role of miR-181a in DLBCL pathogenesis.
  • To identify potential target genes of miR-181a in DLBCL.
  • To elucidate the mechanism by which miR-181a affects ABC-like DLBCL.

Main Methods:

  • Quantitative real-time PCR to measure miR-181a and CARD11 expression.
  • Cell culture and transfection of DLBCL cell lines (OCI-LY10, U2932).
  • Overexpression of miR-181a and CARD11, dual luciferase reporter assays, and nude mouse xenograft models.

Main Results:

  • miR-181a levels were significantly lower in ABC-like DLBCL cells compared to GCB-like DLBCL cells.
  • Overexpression of miR-181a in ABC-like DLBCL cells led to cell cycle arrest, increased apoptosis, and reduced invasiveness.
  • CARD11 was identified as a direct target of miR-181a, and its repression by miR-181a inhibited ABC-like DLBCL growth and metastasis in vitro and in vivo.

Conclusions:

  • miR-181a functions as a tumor suppressor in ABC-like DLBCL.
  • The miR-181a/CARD11 axis is a critical regulator of ABC-like DLBCL progression.
  • Targeting miR-181a or its downstream effectors may offer a therapeutic strategy for DLBCL.

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