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Carcinogenesis. 2018 Sep 21;39(9):1185-1196. doi: 10.1093/carcin/bgy092.

MicroRNA-498 promotes proliferation and migration by targeting the tumor suppressor PTEN in breast cancer cells.

Author information

1
Department of Laboratory Medicine and Pathology, Heritage Medical Research Center, University of Alberta, Edmonton, Alberta, Canada.
2
Department of Oncology, Cross Cancer Institute, University Ave., University of Alberta, Edmonton, Alberta, Canada.

Abstract

Triple negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and high mortality rate. The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays an important role in cell proliferation and cell migration by negatively regulating the PI3K/Akt pathway. PTEN is downregulated by microRNAs in multiple cancers. However, few microRNAs have been reported to directly target PTEN in TNBC. In this study, microRNAs predicted to target PTEN were screened by immunoblotting and luciferase reporter assays. Expression levels of microRNA-498 (miR-498) were measured by TaqMan microRNA assays. We performed clonogenic, cell cycle and scratch wound assays to examine the oncogenic role of miR-498. We demonstrated that miR-498 directly targeted the 3'untranslated region of PTEN mRNA and reduced PTEN protein levels in TNBC cells. Compared with the non-tumorigenic breast epithelial cell line MCF-10A, TNBC cell lines overexpressed miR-498. Moreover, miR-498 promoted cell proliferation and cell cycle progression in TNBC cells in a PTEN-dependent manner. Suppressing miR-498 overexpression impaired the oncogenic effects of miR-498 on cell proliferation and cell migration. This study identified a novel microRNA (miR-498) overexpressed in TNBC cells and its oncogenic role in suppressing PTEN. These results provide new insight into the downregulation of PTEN and indicate a potential therapeutic target for treating TNBC.

PMID:
29985991
PMCID:
PMC6148990
[Available on 2019-09-21]
DOI:
10.1093/carcin/bgy092
[Indexed for MEDLINE]

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