Long Noncoding RNA LINC01133 Confers Tumor-Suppressive Functions in Ovarian Cancer by Regulating Leucine-Rich Repeat Kinase 2 as an miR-205 Sponge

Am J Pathol. 2019 Nov;189(11):2323-2339. doi: 10.1016/j.ajpath.2019.07.020.

Abstract

Ovarian cancer represents one of the most commonly occurring malignant tumors among females. Long noncoding RNAs act as biomarkers associated with the pathophysiology of multiple kinds of malignancies, including ovarian cancer. This study aimed to clarify the molecular mechanism of LINC01133 in the progression of ovarian cancer. Initially, microarray-based analysis was used to screen differentially expressed long noncoding RNAs and miRNAs, with LINC01133 and miR-205 obtained for this study. The biological functions of LINC01133, miR-205, and leucine-rich repeat kinase 2 (LRRK2) were validated on cell proliferation, migration, and invasion of ovarian cancer through gain-of-function and loss-of-function experiments. Finally, tumorigenesis was measured in vivo by inducing tumor xenograft in nude mice. The findings revealed a poor expression of LINC01133 in ovarian cancer tissue and cell, which was predominantly expressed in the cytoplasm. LINC01133 repressed cell proliferation, invasion, migration, and tumorigenic ability. miR-205 targeted and negatively regulated LRRK2. LINC01133 was also found to function as an miR-205 sponge to decrease ovarian cancer cell proliferation, migration, and invasion by elevating LRRK2. These in vitro findings were reproduced in vivo on tumor xenograft in nude mice. In conclusion, because of its role as an miR-205 sponge, LINC01133 repressed the development of ovarian cancer by up-regulating LRRK2.

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing / physiology
  • Genes, Tumor Suppressor / physiology
  • HEK293 Cells
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • RNA, Long Noncoding / physiology*
  • Tumor Cells, Cultured

Substances

  • MIRN205 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA LINC01133, human
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2