LncRNA GACAT3 predicts poor prognosis and promotes cell proliferation in breast cancer through regulation of miR-497/CCND2

Cancer Biomark. 2018;22(4):787-797. doi: 10.3233/CBM-181354.

Abstract

Breast cancer is the most common malignancy in women which increases gradually all over the world. LncRNA GACAT3 has been found to be increased in gastric cancer and associated with tumor malignancy. However, whether GACAT3 plays a role in the regulation of breast cancer is not known. In the present study, we found that GACAT3 expression was increased in breast cancer tissues and cells compared with adjacent normal tissues and normal cells. High GACAT3 expression was correlated with the poor prognosis of breast cancer patients. GACAT3 and cyclin D2 (CCND2) contained a binding site of miR-497. miR-497 was decreased in breast cancer tissues and cells compared with adjacent normal tissues and normal cells. Low miR-497 expression was correlated with the poor prognosis of breast cancer patients. In breast cancer tissues, the expression of miR-497 was negatively correlated with GACAT3. Downregulation of GACAT3 increased miR-497 expression. miR-497 mimic reduced the luciferase of GACAT3 and CCND2. Anti-miR-497 reversed the effects of GACAT3 downregulation. We also found that GACAT3 may act as a ceRNA for miR-497, enhancing the expression of CCND2. In conclusion, GACAT3 promotes breast cancer malignancy by sponging miR-497, leading to the enhancement of its endogenous target CCND2. These results suggest that GACAT3/miR-497/CCND2 is a potential therapeutic target and biomarker for breast cancer.

Keywords: Breast cancer; CCND2; lncRNA GACAT3; malignancy; miR-497.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin D2 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics*

Substances

  • CCND2 protein, human
  • Cyclin D2
  • MIRN497 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding