Upregulation of hsa_circ_0136666 contributes to breast cancer progression by sponging miR-1299 and targeting CDK6

J Cell Biochem. 2019 Aug;120(8):12684-12693. doi: 10.1002/jcb.28536. Epub 2019 Apr 16.

Abstract

Circular RNAs (circRNAs) can participate in multiple cancers, including breast cancer. Increasing circRNAs are recognized in various cancers because of the high-throughput sequencing. However, the potential physiological effect of hsa_circ_0136666 in breast cancer progression is unknown. In our study, the biological role of hsa_circ_0136666 in breast cancer development was studied. It was displayed that hsa_circ_0136666 was greatly increased in breast cancer. In addition, overexpression of hsa_circ_0136666 was able to promote Michigan Cancer Foundation-7 (MCF7) and BT474 cell proliferation and triggered cell cycle in G2/M phase. microRNA plays critical role in tumor development and they can act as direct targets of circRNAs. miR-1299 has been implicated as a famous tumor suppressor in many cancers. Here, miR-1299 was predicted as the target of hsa_circ_0136666. Meanwhile, its Upregulation repressed breast cancer proliferation, migration and invasion capacity, which could be reversed by the increase of hsa_circ_0136666. Furthermore, Cyclin-dependent kinase 6 (CDK6) was speculated as the downstream target of miR-1299. In MCF7 and BT474 cells, CDK6 was greatly overexpressed and it was shown that CDK6 contributed a lot to breast cancer progression. Subsequently, it was implied that hsa_circ_0136666 could modulate CDK6 levels positively in vitro. In conclusion, it was revealed that Upregulation of hsa_circ_0136666 promoted breast cancer progression by sponging miR-1299 and targeting CDK6.

Keywords: breast cancer; cyclin-dependent kinase 6; hsa_circ_0136666; miR-1299.

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin-Dependent Kinase 6 / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • MIRN1299 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6