Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR-499a-5p/LMX1A/NLRC5 pathway

J Cell Mol Med. 2019 Aug;23(8):5048-5062. doi: 10.1111/jcmm.14362. Epub 2019 Jun 17.

Abstract

Dysregulation of long non-coding RNAs (lncRNAs) confirm that it plays a crucial role in tumourigenesis and malignant progression of glioma. The present study demonstrated that LncRNA secretory carrier membrane protein 1 (SCAMP1) was up-regulated and functioned as an oncogene in glioma cells. In addition, miR-499a-5p was down-regulated meanwhile exerted tumour-suppressive function in glioma cells. Subsequently, inhibition of SCAMP1 significantly restrained the cell proliferation, migration and invasion, as well as promoted apoptosis by acting as a molecular sponge of miR-499a-5p. Transcription factor LIM homeobox transcription factor 1, alpha (LMX1A) was overexpressed in glioma tissues and cells. Moreover, miR-499a-5p targeted LMX1A 3'-UTR in a sequence-specific manner. Hence, down-regulation of SCAMP1 remarkably reduced the expression level of LMX1A, indicating that LMX1A participated in miR-499a-5p-induced tumour-suppressive effects on glioma cells. Furthermore, knockdown of LMX1A decreased NLR family, CARD domain containing 5 (NLRC5) mRNA and protein expression levels through directly binding to the NLRC5 promoter region. Down-regulation of NLRC5 obviously inhibited malignant biological behaviours of glioma cells through attenuating the activity of Wnt/β-catenin signalling pathway. In conclusion, our study clarifies that SCAMP1/miR-499a-5p/LMX1A/NLRC5 axis plays a critical role in modulating malignant progression of glioma cells, which provide a novel therapeutic strategy for glioma treatment.

Keywords: LMX1A; NLRC5; SCAMP1; glioma; long non-coding RNAs; miR-499a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis / genetics
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • LIM-Homeodomain Proteins / genetics*
  • LIM-Homeodomain Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • Wnt Signaling Pathway / genetics

Substances

  • 3' Untranslated Regions
  • Intracellular Signaling Peptides and Proteins
  • LIM-Homeodomain Proteins
  • LMX1A protein, human
  • MicroRNAs
  • NLRC5 protein, human
  • RNA, Long Noncoding
  • SCAMP1 protein, human
  • Transcription Factors
  • Vesicular Transport Proteins