Baicalein inhibits breast cancer growth via activating a novel isoform of the long noncoding RNA PAX8-AS1-N

J Cell Biochem. 2018 Aug;119(8):6842-6856. doi: 10.1002/jcb.26881. Epub 2018 Apr 25.

Abstract

Baicalein, a natural flavonoid, has fascinating anti-cancer properties in breast cancer. Long noncoding RNAs (lncRNAs), a class of transcripts with no protein-coding potential, also exhibit critical roles in breast cancer. However, the molecular mechanisms mediating the anti-cancer properties of baicalein and whether lncRNAs are involved in the anti-cancer effects are still unclear. In this study, we identified a novel isoform of lncRNA PAX8-AS1 (PAX8-AS1-N), which is activated by baicalein in a dose- and time-dependent manner. Functional assays showed that PAX8-AS1-N reduced cell viability, inhibited cell-cycle progression, and induced apoptosis of breast cancer cells in vitro. Depletion of PAX8-AS1-N promoted breast xenograft tumor growth in vivo. Furthermore, depletion of PAX8-AS1-N attenuated the suppressive roles of baicalein on cell viability, the apoptosis induced by baicalein, and also the suppressive roles of baicalein on tumor growth in vivo. Mechanistically, PAX8-AS1-N bound to miR-17-5p, and up-regulated miR-17-5p targets, such as PTEN, CDKN1A, and ZBTB4. In addition, PAX8-AS1-N was down-regulated in breast cancer and reduced expression of PAX8-AS1-N indicated poor survival of breast cancer patients. In conclusion, our results demonstrated that PAX8-AS1-N activation mediated the anti-cancer effects of baicalein via regulating miR-17-5p, and suggested that baicalein and enhancing PAX8-AS1-N would be potential therapeutic strategies against breast cancer.

Keywords: baicalein; breast cancer; long noncoding RNA; microRNA; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Female
  • Flavanones / pharmacology*
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • RNA Isoforms* / genetics
  • RNA Isoforms* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Neoplasm* / genetics
  • RNA, Neoplasm* / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Flavanones
  • MIRN17 microRNA, human
  • MicroRNAs
  • RNA Isoforms
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • long non-coding RNA PAX8-AS1, human
  • baicalein