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SETD5 Promotes Tumor Progression and Induces Cancer Stem Cell-Like Properties Through Upregulation of AKT1 Signaling in Breast Cancer
58 Pages Posted: 4 Apr 2020More...
A variety of studies have revealed the role of SET domain-containing 5 (SETD5) in post translational modifications of non-histone proteins. Although it was reported that SETD5 gene mutation is associated with the tumor progression in the several types of human cancer, including breast cancer (BC), its functional role in BC progression has not been fully elucidated. In the present study, we investigated the clinical significance and the functional role of SETD5 in BC. Our studies show that SETD5 expression in BC was correlated with poor clinical outcomes, including lymph mode metastasis and advanced clinical stage. SETD5 was an independent predictor of poor overall survival in BC. Further, our studies show that down-regulation of SETD5 significantly decreased BC cell proliferation, metastasis, angiogenesis and cancer stem cells-like (CSCs) properties, and increased apoptosis of BC cells. In addition, in vivo experiments show that blocking of SETD5 expression significantly inhibited tumor formation and lung metastases of BC cells. SETD5 regulates glycolysis of breast CSCs Mechanistic analysis showed that SETD5 contributes BC progression by interacting with AKT1 pathway. These findings indicate SETD5 is a potential prognosis marker and interventional target for the treatment of BC.
Funding Statement: This study was supported by the National Natural Science Fundation of China (81760531).
Declaration of Interests: The authors declare no conflict of interest.
Ethics Approval Statement: This research complied with the Declaration of Helsinki and was approved by the Human Ethics Committee and the Research Ethics Committee of Yanbian University.
All animal experiments were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Yanbian University Animal Care & Use Committee.
Keywords: Breast cancer; SETD5; Prognosis; Tumor progression; Cancer stem celllike; AKT1 Signaling
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