LINC00998 functions as a novel tumor suppressor in acute myeloid leukemia via regulating the ZFP36 ring finger protein/mammalian target of rapamycin complex 2 axis

Bioengineered. 2021 Dec;12(2):10363-10372. doi: 10.1080/21655979.2021.1996506.

Abstract

Acute myeloid leukemia (AML) is a severe hematologic malignancy that threatens human health. Long non-coding RNA (lncRNA) is emerged as a key player in human cancer. Herein, we explored the role of LINC00998 in human AML. LINC00998 was significantly decreased in human AML, which was linked to relapse and poor prognosis. Stable overexpression of LINC00998 inhibited AML cell viability, colony ability, DNA synthesis rate and increased apoptosis. LINC00998 was mainly located in the cytoplasm, in which interacted with ZFP36 ring finger protein (ZFP36), a mRNA destabilizing factor, resulting in increased decay of mammalian target of rapamycin complex 2 (mTORC2), a well-known proto-oncogene in AML. Overexpression of mTORC2 partly blocked the tumor suppressive effects of LINC00998. Importantly, LINC00998 shortened in vivo AML cell survival in xenograft tumor model. Taken together, we found that LINC00998 is a novel tumor-inhibiting lncRNA in human AML. The dysregulation of LINC00998/ZFP36/mTORC2 axis is linked to leukemogenesis and progression.

Keywords: LncRNA; acute myeloid leukemia; mRNA decay; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Child
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Leukemic
  • Genes, Tumor Suppressor*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Mechanistic Target of Rapamycin Complex 2 / genetics*
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Mice
  • Mice, Nude
  • Protein Binding / genetics
  • RNA Stability / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tristetraprolin / genetics*
  • Tristetraprolin / metabolism

Substances

  • RNA, Long Noncoding
  • Tristetraprolin
  • ZFP36 protein, human
  • Mechanistic Target of Rapamycin Complex 2

Grants and funding

This study was approved by Shenzhen Science and Technology Project, Guangdong Province, China (Grant no. JCYJ20160429180540076).