circSLC8A1 sponges miR-671 to regulate breast cancer tumorigenesis via PTEN/PI3k/Akt pathway

Genomics. 2021 Jan;113(1 Pt 1):398-410. doi: 10.1016/j.ygeno.2020.12.006. Epub 2020 Dec 8.

Abstract

Breast cancer is the most frequently diagnosed and the leading cause of cancer-related deaths in women worldwide. However, the role of circSLC8A1 in breast cancer remains elusive. Herein, a cohort of 77 breast tumors and paired adjacent normal mammary tissues were collected. We demonstrated that circSLC8A1 was significantly down-regulated in breast cancer tissues and cell lines, of which expression was negatively correlated with clinical severity and dismal prognosis. Overexpression of circSLC8A1 suppressed cell proliferation, migration and invasion in vitro, and inhibited tumor growth in vivo. CircSLC8A1 directly targeted miR-671 to execute tumor suppressive activities via regulating PI3k/Akt signaling. Krüppel-like factor 16 (KLF16), a transcriptional activator of PTEN, was identified as a target of miR-671. Furthermore, circSLC8A1 could sponge miR-671 to suppress breast tumor growth via PTEN/PI3k/Akt signaling in vivo. In summary, circSLC8A1/miR-671 regulates breast cancer progression through PTEN/PI3k/Akt signaling, which may provide efficient therapeutic target for this devastating cancer.

Keywords: Breast cancer; KLF16; PTEN; circSLC8A1; miR-671.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Cell Line
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kruppel-Like Transcription Factors / metabolism
  • MCF-7 Cells
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Signal Transduction
  • Sodium-Calcium Exchanger / genetics*

Substances

  • KLF16 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN671 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Sodium-Calcium Exchanger
  • sodium-calcium exchanger 1
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase