miR‑338‑3p suppresses the malignancy of T‑cell lymphoblastic lymphoma by downregulating HOXA3

Mol Med Rep. 2019 Sep;20(3):2127-2134. doi: 10.3892/mmr.2019.10451. Epub 2019 Jul 1.

Abstract

T‑cell lymphoblastic lymphoma (T‑LBL) is an aggressive malignancy with poor prognosis due to frequent relapses. Previous studies have reported an association of the disease with abnormal chromosomal rearrangements, DNA copy number alterations and mutations in critical signaling factors, such as those in the Notch1 pathway; however, the molecular mechanisms underlying the development of the disease remain unclear, limiting the development of novel therapies. In the present study, gene expression was detected by qPCR and western blot analysis. Diagnostic analysis was performed by ROC curve. Cell proliferation, invasion and migration were analyzed by cell proliferation and Transwell assays. Gene interactions were analyzed using luciferase reporter assay. In the present study, it was observed that the expression levels of microRNA‑338‑3p (miR‑338‑3p) were reduced in patient lymphoma tissues and a T‑LBL cell line. Upregulation of its expression inhibited the migration and proliferation of cultured T‑LBL cells. Bioinformatics analysis of putative target mRNAs of miR‑338‑3p identified a direct binding site in the 3'‑untranslated of homeobox A3 (HOXA3). The levels of HOXA3 mRNA and protein were associated with those of miR‑338‑3p, and overexpression of HOXA3 promoted the malignant phenotype of T‑LBL cells. The results suggested that miR‑338‑3p may suppress the development of T‑LBL via the downregulation of oncogenic factors, such as HOXA3. The findings indicated that further investigation into miR‑338‑3p and the HOXA3 regulatory network may aid the development of novel therapeutic tools.

MeSH terms

  • Adult
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Leukemic*
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*

Substances

  • HOXA3 protein, human
  • Homeodomain Proteins
  • MIRN338 microRNA, human
  • MicroRNAs