A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion

Cancer Immunol Res. 2016 Apr;4(4):337-44. doi: 10.1158/2326-6066.CIR-15-0161. Epub 2016 Feb 9.

Abstract

MicroRNAs are endogenous noncoding RNAs that play important roles in a wide variety of biologic processes such as apoptosis, development, aging, and tumorigenesis. The B-cell lymphoma 6 (BCL6) transcriptional repressor has emerged as a critical therapeutic target in diffuse large B-cell lymphomas (DLBCL), but the mechanisms regulating BCL6 are still unclear. In the current study, we screened the microRNA expression profiles in DLBCL specimens and cell lines by qRT-PCR and found that the expression of miR-144 was significantly downregulated in DLBCL tissues and cell lines and negatively correlated with BCL6 expression. We further demonstrated that BCL6 was the direct target gene of miR-144, and miR-144 suppressed the expression of BCL6 via binding the 3'untranslated region of BCL6 mRNA. Biologically, forced expression of miR-144 significantly attenuated cell proliferation and invasion of OCI-Ly3 cells in vitro, and the tumor-suppressor effect of miR-144 was also confirmed using a xenograft mouse model in vivo Taken together, our results reveal that miR-144 regulates BCL6 in DLBCL and provide a rationale for developing strategies that target miR-144 as a therapeutic intervention for DLBCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics
  • Disease Models, Animal
  • Gene Expression
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • MIRN144 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger