HOXD-AS1/miR-130a sponge regulates glioma development by targeting E2F8

Int J Cancer. 2018 Jun 1;142(11):2313-2322. doi: 10.1002/ijc.31262. Epub 2018 Jan 31.

Abstract

Glioma development is an extremely complex process with changes occurring in numerous genes. HOXD antisense growth-associated long noncoding RNA (HOXD-AS1), an important long noncoding RNA (lncRNA), is known to regulate metastasis-related gene expression in bladder cancer, ovarian cancer and neuroblastoma. Here, we elucidated the function and possible molecular mechanisms of lncRNA HOXD-AS1 in human glioma cells. Our results proved that HOXD-AS1 expression was upregulated in glioma tissues and in glioma cell lines. HOXD-AS1 overexpression promoted cell migration and invasion in vitro, whereas knockdown of HOXD-AS1 expression repressed these cellular processes. Mechanistic studies further revealed that HOXD-AS1 could compete with the transcription factor E2F8 to bind with miR-130a, thus affecting E2F8 expression. Additionally, reciprocal repression was observed between HOXD-AS1 and miR-130a, and miR-130a mediated the tumor-suppressive effects of HOXD-AS1 knockdown. Taken together, these results provide a comprehensive analysis of the role of HOXD-AS1 in glioma cells and offer important clues to understand the key roles of competing endogenous RNA (ceRNA) mechanisms in human glioma.

Keywords: E2F8; HOXD-AS1; ceRNA; lncRNA; miR-130a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Grading
  • Neoplasm Metastasis
  • RNA Interference*
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction

Substances

  • E2F8 protein, human
  • MIRN130 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • long non-coding RNA HOXD-AS1, human