MicroRNA-211 attenuates cell proliferation in T-cell lymphoblastic lymphoma through targeting TCF12

Leuk Res. 2021 Nov:110:106653. doi: 10.1016/j.leukres.2021.106653. Epub 2021 Jun 29.

Abstract

T-cell lymphoblastic lymphoma (T-LBL) is a class of highly aggressive hematologic neoplasms originating from progenitor T-lymphocytes. MicroRNA (miRNA) is an endogenous RNA molecule with 22 nucleotides in length. Accumulated evidence suggests that miRNA functions as a key regulator in human cancer. Herein, by in silico analysis, we found that miR-211 was a decreased miRNA in T-LBL in high-throughput sequencing data, which was subsequently verified in our cohort. Low miR-211 was closely correlated with bulky disease, high ann arbor stage, relapse and poor prognosis. miR-211 was regulated by N6-methyladenosine (m6A) modification, specifically, m6A methyltransferase METTL14 methylated primary miR-211 (pri-miR-211), expediting pri-miR-211 processing via recruiting DGCR8. Functionally, miR-211 overexpression significantly reduced T-LBL cell viability, DNA synthesis rate and spheroid formation ability, whereas silencing of miR-211 had the opposite effects. In addition, we established the xenograft tumor model and found that miR-211 remarkably inhibited tumor growth in vivo. Further, TCF12 was the direct target of miR-211, miR-211 bound to TCF12 mRNA 3`-untranslated region (UTR) and increased its decay, overexpression of TCF12 could effectively rescue the weakened malignant behavior of T-LBL cells caused by miR-211 overexpression. Collectively, our data clearly demonstrate that miR-211 is a novel tumor suppressor in T-LBL, targeting of miR-211/TCF12 axis may be a potential treatment for T-LBL patients.

Keywords: N6-methyladenosine; Prognosis; T-cell lymphoblastic lymphoma; miR-211; miRNA processing.

MeSH terms

  • Adult
  • Animals
  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • MIRN211 microRNA, human
  • MicroRNAs
  • TCF12 protein, human