NANOG gene suppression and replacement of let-7 modulate the stemness, invasion, and apoptosis in breast cancer

Gene. 2021 Oct 30:801:145844. doi: 10.1016/j.gene.2021.145844. Epub 2021 Jul 16.

Abstract

In the treatment of breast cancer (BC), as an important type of cancer in women, the specific cells, called cancer stem cells (CSCs), are the reason of failure and metastasis. So, targeting CSCs can be used as a novel strategy in cancer therapy in addition to common therapeutic strategies. According to the importance of CSCs, we tried to find a correlation between stemness and metastatic characteristics of BC cells, to address whether CSCs are a potential target for cancer therapy. Here, we evaluated the NANOG inhibition by siRNA and the increase of Let-7a levels by miRNA mimic in breast cancer cells and the effects of these changes on biologic aspects like cell apoptosis, stemness and invasion. Our results showed that the inhibition of NANOG combined with Let-7a restoration contributed to significant decrease in malignant phenotypes and stemness feature of BC cells. In conclusion, these findings showed that the combination of Let-7a miRNA mimic and Nanog siRNA could be exploited as a new treatment strategy to improve the cancer therapy outcome.

Keywords: Apoptosis; Breast cancer; Let-7; Migration; NANOG; Stemness.

MeSH terms

  • Antigens, CD / genetics
  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HMGA2 Protein / genetics
  • Humans
  • MicroRNAs / genetics*
  • Nanog Homeobox Protein / genetics*
  • Nanog Homeobox Protein / metabolism
  • Neoplastic Stem Cells / pathology
  • Octamer Transcription Factor-3 / genetics
  • RNA, Small Interfering
  • RNA-Binding Proteins / genetics
  • Spheroids, Cellular / pathology
  • Transfection
  • Vimentin / genetics

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • HMGA2 Protein
  • HMGA2 protein, human
  • Lin28A protein, human
  • MicroRNAs
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • VIM protein, human
  • Vimentin
  • mirnlet7 microRNA, human