Knockdown of lncRNA HOXD-AS1 suppresses proliferation, migration and invasion and enhances cisplatin sensitivity of glioma cells by sponging miR-204

Biomed Pharmacother. 2019 Apr:112:108633. doi: 10.1016/j.biopha.2019.108633. Epub 2019 Feb 20.

Abstract

Increasing evidence suggests the involvement of long noncoding RNAs (lncRNAs) in various biological process including cancer progression and drug resistance. LncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) had been demonstrated to act as an oncogenic gene, contributing to the development and progression of several cancers. However, its functional role and molecular mechanism underlying glioma progression and cisplatin (DDP) resistance has not been well elucidated. In this study, we found that HOXD-AS1 was up-regulated in glioma tissues and cells and negatively correlated with survival time. HOXD-AS1 knockdown suppressed proliferation, migration and invasion as well as enhanced DDP sensitivity of glioma cells. Moreover, HOXD-AS1 could function as a miR-204 sponge in glioma cells. Overexpression of miR-204 could mimic the functional role of down-regulated HOXD-AS1 in glioma cells. Furthermore, miR-204 inhibition reversed the effect of HOXD-AS1 knockdown on cancer progression and DDP sensitivity of glioma cells. In conclusion, knockdown of HOXD-AS1 suppressed proliferation, migration and invasion and enhanced DDP sensitivity of glioma cells through sequestering miR-204, providing a promising therapeutic target for glioma patients.

Keywords: Cisplatin; Glioma; HOXD-AS1; Migration and invasion; Proliferation; miR-204.

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Cell Proliferation / drug effects*
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN204 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA HOXD-AS1, human
  • Cisplatin