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

Affiliation

Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin's Clinical Research Center for Cancer, China. Electronic address: [Email]

Abstract

UNASSIGNED : 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.
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.
RESULTS : 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.
CONCLUSIONS : 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,