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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.

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



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.


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.


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.


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.


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

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