In vivo and in vitro impact of miRNA-153 on the suppression of cell growth apoptosis through mTORC2 signaling pathway in breast cancer

J Recept Signal Transduct Res. 2022 Aug;42(4):390-398. doi: 10.1080/10799893.2021.1970766. Epub 2021 Aug 29.

Abstract

Purpose: To investigate the effects and mechanism of miRNA-153 on breast cancer cells in vitro and in vivo.

Material and methods: The cells and mice were divided into five groups: miRNA-153 mimic, miRNA-153 NC, miRNA-153 inhibitor, miRNA-153 inhibitor-NC, and blank control groups. The real-time PCR and western blot were used to detect the rictor expression regulated by miRNA-153. The western blot was used to explore the expression levels of p-Akt Ser473, p-SGK1 Ser422, and p-FOXO1 Thr24 regulated by miRNA-153. The H&E stain was used to detect the morphology and vitality of tumor cells. Flow cytometry analysis or TUNEL detection was used to evaluate the apoptosis of tumor cells.

Results: MiRNA-153 was significantly reduced in breast cancer cell lines. The real-time PCR and western blot assay suggested that the miRNA-153 downregulation of rictor expression, which was correlated with the antitumor effects both in vitro and in vivo. The western blot assay also showed that the expression levels of p-Akt Ser473, p-SGK1 Ser422, and p-FOXO1 Thr24 were largely reduced in miRNA-153 treated group, which indicated that miRNA-153 inhibited breast cancer growth by regulation of mTORC2 signaling pathway. The H&E stain demonstrated that the morphology and vitality of tumor cells in tumor tissues were influenced in miRNA-153 mimic treated group. The TUNEL detection also showed a great quantity of apoptotic cells in the miRNA-153 mimic group.

Conclusions: All these results uncovering that the miRNA-153 inhibited breast cancer growth via regulation of mTORC2 signaling pathway, which provided breast cancer treatment a novel direction.

Keywords: Anti-breast cancer; apoptosis; mTORC2 signaling pathway; miRNA-153.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Mechanistic Target of Rapamycin Complex 2 / genetics
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Mice
  • MicroRNAs* / metabolism
  • Neoplasms*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • MIRN153 microRNA, mouse
  • MicroRNAs
  • Mechanistic Target of Rapamycin Complex 2
  • Proto-Oncogene Proteins c-akt