LncRNA-NEAT1 promotes proliferation of T-ALL cells via miR-146b-5p/NOTCH1 signaling pathway

Pathol Res Pract. 2020 Nov;216(11):153212. doi: 10.1016/j.prp.2020.153212. Epub 2020 Sep 13.

Abstract

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant tumor of the hematopoietic system, which can develop at any age, with the symptoms of weakness, fatigue, enlarged lymph nodes, or weight loss. Nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in the process of T-ALL, but the regulatory mechanism is still not known clearly.

Methods: The expression levels of NEAT1 and miR-146b-5p in T-ALL cells were performed by qRT-PCR and NOTCH1 protein level- wwWwas determined by western blot assay. Dual-luciferase reporter assay was used to detect the interaction between NEAT1 and miR-146b-5p, as well as miR-146b-5p and NOTCH1. The cell proliferation was measured by using MTT assay and colony formation assay.

Results: The expression levels of NEAT1 were markedly increased, but miR-146b-5p levels were reduced in T-ALL cells. Knockdown of NEAT1 or overexpression of miR-146b-5p decreased NOTCH1 expression, inhibited the proliferation of T-ALL cells. MiR-146b-5p bound both NEAT1 and NOTCH1 3'-UTR directly. Finally, inhibition of miR-146b-5p could abrogate the effects of NEAT1 knockdown on the proliferation of T-ALL cells.

Conclusion: NEAT1 promotes the proliferation of T-ALL cells by sponging miR-146b-5p to upregulate the expression of NOTCH1. The results of this study provide new insight into the action mechanism of NEAT1 modulating T-ALL progression.

Keywords: NEAT1; NOTCH1; Proliferation; T-ALL; miR-146b-5p.

MeSH terms

  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cell Proliferation / physiology*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • RNA, Long Noncoding / metabolism*
  • Receptor, Notch1 / metabolism*
  • Signal Transduction / physiology*

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptor, Notch1