lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

SETD5 Promotes Tumor Progression and Induces Cancer Stem Cell-Like Properties Through Upregulation of AKT1 Signaling in Breast Cancer

58 Pages Posted: 4 Apr 2020

See all articles by Zhaoting Yang

Zhaoting Yang

Yanbian University - Department of Pathology

Chengye Zhang

Yanbian University - Department of Pathology

Nan Che

Yanbian University - Department of Pathology

Ying Feng

Yanbian University - Department of Pathology

Chao Li

Yanbian University - Institute for Regenerative Medicine

Yanhua Xuan

Yanbian University - Department of Pathology

More...

Abstract

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

Suggested Citation

Yang, Zhaoting and Zhang, Chengye and Che, Nan and Feng, Ying and Li, Chao and Xuan, Yanhua, SETD5 Promotes Tumor Progression and Induces Cancer Stem Cell-Like Properties Through Upregulation of AKT1 Signaling in Breast Cancer (3/3/2020). Available at SSRN: https://ssrn.com/abstract=3550004 or http://dx.doi.org/10.2139/ssrn.3550004

Zhaoting Yang

Yanbian University - Department of Pathology

Yanji, 133002
China

Chengye Zhang

Yanbian University - Department of Pathology

Yanji, 133002
China

Nan Che

Yanbian University - Department of Pathology

Yanji, 133002
China

Ying Feng

Yanbian University - Department of Pathology

Yanji, 133002
China

Chao Li

Yanbian University - Institute for Regenerative Medicine

Yanji, 133002
China

Yanhua Xuan (Contact Author)

Yanbian University - Department of Pathology ( email )

Yanji, 133002
China

Click here to go to TheLancet.com

Paper statistics

Abstract Views
370
Downloads
66
PlumX Metrics