LncRNA HAND2-AS1 exerts anti-oncogenic effects on ovarian cancer via restoration of BCL2L11 as a sponge of microRNA-340-5p

J Cell Physiol. 2019 Dec;234(12):23421-23436. doi: 10.1002/jcp.28911. Epub 2019 Jun 21.

Abstract

In the early stage of ovarian cancer (OC), molecular biomarkers are critical for its diagnosis and treatment. Nevertheless, there is little research on the mechanism underlying tumorigenesis in OC. Herein, we aimed to explore whether long noncoding RNA (lncRNA) HAND2-AS1 participated in the regulation of the cell proliferation, migration, and apoptosis of OC by regulating B-cell lymphoma 2 like 11 (BCL2L11) and microRNA-340-5p (miR-340-5p). Differentially expressed lncRNAs in OC were screened by microarray-based analysis. HAND2-AS1, BCL2L11, and miR-340-5p expression was assessed in normal ovarian and OC tissues and human OC cell lines. Then, the relationships among HAND2-AS1, BCL2L11, and miR-340-5p were explored. Ectopic expression and depletion experiments were applied to analyze the effects of HAND2-AS1, miR-340-5p and BCL2L11 on migration, invasion, and proliferation of OC cells, as well as apoptosis. Lastly, the tumor xenograft in nude mice was conducted to test the tumorigenesis in vivo. In silico analysis displayed poor expression of HAND2-AS1 in OC. HAND2-AS1 specifically sponged with miR-340-5p which was found to directly target BCL2L11. Importantly, HAND2-AS1 or BCL2L11 overexpression or miR-340-5p downregulation resulted in reduction of cell invasion and migration, together with decrease of cell proliferation and increase of cell apoptosis in OC. Besides, high-expressed HAND2-AS1 inhibited the tumorigenesis in nude mice. To sum up, these data suggests HAND2-AS1 as an anti-oncogene in OC through upregulation of BCL2L11 by competitively binding to miR-340-5p, which demonstrates that there are potential diagnosis and therapy values of HAND2-AS1 in OC.

Keywords: BCL2L11; apoptosis; invasion; lncRNA HAND2-AS1; microRNA-340-5p; migration; ovarian cancer; proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Bcl-2-Like Protein 11 / genetics
  • Bcl-2-Like Protein 11 / metabolism*
  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Tumor Burden

Substances

  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • MIRN340 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA HAND2-AS1, human