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Cell Physiol Biochem. 2018;47(5):2126-2135. doi: 10.1159/000491523. Epub 2018 Jul 5.

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5.

Author information

1
Department of Clinical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
2
Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
3
Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
4
Department of Pathology, Anyang Tumor Hospital, Anyang, China.
5
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
6
Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Abstract

BACKGROUND/AIMS:

MicroRNAs (miRNAs) regulate the expressions of cancer-related genes, and are involved in the development and progression of various human cancers. Here, we performed further analyses to determine whether let-7d is functionally linked to Jab1 in breast cancer.

METHODS:

In situ hybridization and immunohistochemical analyses were used to determine the level of let-7d and Jab1 in breast cancer clinical specimens and its correlation with clinicopathological data. Let-7d overexpressing breast cancer cell lines combined with mouse models bearing cell-derived xenografts were used to assess the functional role of let-7d both in vitro and in vivo.

RESULTS:

In this study, we found that let-7d was downregulated in breast cancer tissues, coupled with the elevations of Jab1 protein expressions, compared with paired adjacent noncancerous breast tissues. Let-7d overexpression significantly suppressed the proliferation and invasion in MCF-7 and MDA-MB-231 cells. Dual luciferase reporter assay indicated that Jab1 was the direct target of let-7d. Stepwise studies from in vitro and in vivo experiments indicated that let-7d overexpression inhibited cell growth and decreased Jab1 expressions in breast cancer cells and nude mice tumor tissues. Statistical analyses demonstrated that breast cancer patients with low levels of let-7d or high levels of Jab1 had a significant correlation with worse prognosis.

CONCLUSION:

These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients.

KEYWORDS:

Biomarker; Breast cancer; COPS5; CSN5; Jab1; Let-7d

PMID:
29975923
DOI:
10.1159/000491523
[Indexed for MEDLINE]
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