miRNA‑135a regulates Hut78 cell proliferation via the GATA‑3/TOX signaling pathway

Mol Med Rep. 2019 Mar;19(3):2361-2367. doi: 10.3892/mmr.2019.9885. Epub 2019 Jan 22.

Abstract

The present study investigated the role of microRNA‑135a (miR‑135a) in cutaneous T‑cell lymphoma (CTCL) proliferation. Compared with the normal T lymphocyte control cell line, the mRNA and protein levels of GATA binding protein 3 (GATA‑3) were markedly increased in the Hut78 cell line and miR‑135a was markedly decreased (P<0.05). Based on bioinformatics, the target gene of miR‑135a was identified as GATA‑3. Dual luciferase and pre‑miR‑135a assays showed that miR‑135a regulated the translation of GATA‑3. In addition, the overexpression of miR‑135a mimics decreased the protein levels of GATA‑3 and thymocyte selection‑associated high mobility group box (TOX). The substantially increased mRNA and protein levels of GATA‑3 may be associated with the downregulation of miR‑135a, leading to T‑cell deregulation and proliferation through GATA‑3/TOX regulation and subsequently causing CTCL.

Keywords: microRNA-135a; GATA binding protein 3; cutaneous T-cell lymphoma; thymocyte selection-associated high mobility group box.

MeSH terms

  • Cell Line
  • Cell Proliferation
  • GATA3 Transcription Factor / genetics*
  • GATA3 Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic*
  • High Mobility Group Proteins / genetics*
  • High Mobility Group Proteins / metabolism
  • Humans
  • Lymphoma, T-Cell, Cutaneous / genetics*
  • Lymphoma, T-Cell, Cutaneous / metabolism
  • Lymphoma, T-Cell, Cutaneous / pathology
  • MicroRNAs / genetics*
  • Signal Transduction*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • GATA3 Transcription Factor
  • GATA3 protein, human
  • High Mobility Group Proteins
  • MIRN135 microRNA, human
  • MicroRNAs
  • TOX protein, human