LncRNA LINC01446 promotes glioblastoma progression by modulating miR-489-3p/TPT1 axis

Biochem Biophys Res Commun. 2018 Sep 10;503(3):1484-1490. doi: 10.1016/j.bbrc.2018.07.067. Epub 2018 Jul 17.

Abstract

Accumulating evidence indicates that long noncoding RNA (lncRNA) is implicated in human diseases, including cancers. However, how lncRNA regulates glioblastoma (GBM) progression is poorly understood. Our study revealed a novel lncRNA LINC01446 whose expression was elevated in GBM tissues. Besides, high expression of LINC01446 indicated a poor prognosis in GBM patients. Functionally, LINC01446 knockdown dramatically inhibited GBM cell proliferation, arrested cell-cycle progression and attenuated invasion in vitro. Furthermore, the xenograft mouse model showed that LINC01446 silence led to impaired tumor growth in vivo. Mechanistically, bioinformatics analysis showed that LINC01446 acted as a sponge for miR-489-3p which targeted TPT1. Though inhibiting miR-489-3p availability, LINC01446 promoted TPT1 expression in GBM cells. Rescue experiments demonstrated that restoration of TPT1 could significantly rescued the effects of LINC01446 silence or miR-489-3p overexpression. Taken together, this study demonstrates a novel singling pathway of LINC01446/miR-489-3p/TPT1 cascade that regulates GBM progression.

Keywords: Glioblastoma; LINC01446; Long noncoding RNA; TPT1; miR-489-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Disease Progression*
  • Female
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology*
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / metabolism
  • RNA, Long Noncoding / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Protein, Translationally-Controlled 1

Substances

  • Biomarkers, Tumor
  • MIRN489 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TPT1 protein, human
  • Tpt1 protein, mouse
  • Tumor Protein, Translationally-Controlled 1