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Int J Clin Exp Pathol. 2015 May 1;8(5):5017-25. eCollection 2015.

MicroRNA-204 targets JAK2 in breast cancer and induces cell apoptosis through the STAT3/BCl-2/survivin pathway.

Author information

1
Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.

Abstract

MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-204 plays an important role in various human cancers. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated that miR-204 expression level was markedly reduced in both the human breast cancer tissue and cultured breast cancer cell lines (MCF-7, MDA-MB-231). Overexpression of miR-204 inhibited the proliferation and promoted the apoptosis in breast cancer cells, which were reversed by co-transfection of miR-204 inhibitor. We validated that Janus kinase 2 (JAK2), as a direct target of miR-204, is overexpressed in breast cancer. Knockdown of JAK2 suppressed cell viability and induced apoptosis in breast cancer cells. Moreover, the level of miR-204 is negatively correlated with p-STAT3 and anti-apoptotic genes BCl-2 and surviving in breast cancer. In conclusions, miR-204 targets JAK2 and suppressed JAK2 and p-JAK2 expression in breast cancer, which further inhibit the activation of STAT3, BCl-2 and survivin. These findings indicate that manipulation of miR-204 expression may represent a novel therapeutic strategy in the treatment of breast cancer.

KEYWORDS:

Breast cancer; JAK2; apoptosis; miR-204; proliferation

PMID:
26191195
PMCID:
PMC4503067
[Indexed for MEDLINE]
Free PMC Article

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