MicroRNA-22 inhibits proliferation, invasion and metastasis of breast cancer cells through targeting truncated neurokinin-1 receptor and ERα

Life Sci. 2019 Jan 15;217:57-69. doi: 10.1016/j.lfs.2018.11.057. Epub 2018 Nov 28.

Abstract

Heading aims: This topic aims to clarify whether miR-22 directly targets and downregulates the expression of ERα and NK1R-Tr to inhibit the malignant behaviors of breast cancer cells.

Materials and methods: RT-PCR and Western Blotting were used to detect the expression profile of miR-22, NK1R-Tr and ERα. Luciferase reporter assay and CHIP experiment were conducted to investigate the regulation network between miR-22, NK1R-Tr and ERα. MCF-7-ERαI and MDA-MB-231-ERα cell lines were constructed to study the biological behaviors. The SP-NK1R-ERK1/2 signaling pathway was analyzed using Western Blotting. The subcutaneous and metastases tumor models were employed to study the effects of miR-22 on cell proliferation and metastasis of breast cancer cells in vivo.

Key findings: MiR-22 expression level was significantly lower in breast cancerous tissues and cell lines than the adjacent normality, while that of NK1R-Tr increased. The ERα could positively regulate NK1R-Tr expression at DNA level. The descent degree of NK1R-Tr in MCF-7-ERαI cells was far less than that in wild MCF-7 cells, while the findings in MDA-MB-231-ERα cells was more apparent than wild MDA-MB-231 cells. The malignant phenotype was decreased in miR-22 overexpressing cells compared with the wild type. The peak of ERK1/2 phosphorylation was delayed and weakened in miR-22 overexpressing MCF-7 cells, which was agreed with the findings using NK1R-Tr antagonist. The size and number of metastatic tumors declined compared to the controls.

Significance: MiR-22 downregulated the expression of NK1R-Tr and ERα to delay and weaken phosphorylation of ERK1/2 to inhibit proliferation and metastasis of breast cancer cells.

Keywords: Breast cancer; ERα; Invasion; Neurokinin-1 receptor; Proliferation; microRNA-22.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Receptors, Neurokinin-1 / genetics*

Substances

  • Estrogen Receptor alpha
  • MIRN22 microRNA, human
  • MicroRNAs
  • Receptors, Neurokinin-1