Long non-coding RNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer

Cancer Sci. 2018 May;109(5):1428-1446. doi: 10.1111/cas.13552. Epub 2018 Apr 29.

Abstract

The present study aimed to investigate the effect of long non-coding RNA (lncRNA) RP11-552M11.4 on cell proliferation, apoptosis, migration and invasion as well as its targeting genes in epithelial ovarian cancer (EOC) cells. LncRNA RP11-552M11.4 expression was detected in 67 tumor tissues and paired adjacent tissues obtained from EOC patients. lncRNA RP11-552M11.4 mimic/inhibitor plasmids were transferred into ovarian cancer cells (SKOV3, A-2780) and normal ovarian epithelial cells (IOSE80 cells). In addition, rescue experiment was carried out by transferring BRCA2 inhibitor&lncRNA RP11-552M11.4 inhibitor plasmids into SKOV3 and A-2780 cells. qPCR, western blot, CKK-8, Annexin V/propidium iodide (AV/PI), wound-healing and Matrigel invasion assays were carried out to detect RNA expression, protein expression, cell proliferation, apoptosis, migration, and invasion, respectively. LncRNA RP11-552M11.4 expression was elevated in tumor tissues compared with paired adjacent tissues and correlated with higher pathological grade, International Federation of Gynecology and Obstetrics stage and worse overall survival in EOC patients. LncRNA RP11-552M11.4 promoted SKOV3 cell proliferation, migration and invasion whereas it inhibited apoptosis. Rescue experiment and luciferase reporter assay showed that lncRNA RP11-552M11.4 regulated SKOV3 cells functions through binding BRCA2. Further experiments in A-2780 cells also validated that lncRNA RP11-552M11.4 induced A-2780 cell proliferation while repressing apoptosis by targeting BRCA2. In addition, upregulation of lncRNA RP11-552M11.4 increased IOSE80 cell proliferation, migration and invasion while decreasing apoptosis. In conclusion, lncRNA RP11-552M11.4 correlates with worse prognosis, and promotes cell proliferation, migration, invasion, and inhibits cell apoptosis by down-regulating BRCA2 in EOC.

Keywords: apoptosis; epithelial ovarian cancer; invasion; long non-coding RNA RP11-552M11.4; proliferation.

MeSH terms

  • Adult
  • Aged
  • BRCA2 Protein / genetics*
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Survival Analysis
  • Up-Regulation*

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • RNA, Long Noncoding