Targeted Inhibition of SIRT6 Via Engineered Exosomes Impairs Tumorigenesis and Metastasis in Prostate Cancer

Overview

Journal Theranostics

Date 2021 May 17

PMID 33995674

Citations 48

Authors

Qing Han

Qian Rueben Xie

Fan Li

Yirui Cheng

Tingyu Wu

Yanshuang Zhang

Xin Lu

Alice S T Wong

Jianjun Sha

Weiliang Xia

Affiliations

Soon will be listed here.

Abstract

The treatment for metastatic castration-resistant prostate cancer patients remains a great challenge in the clinic and continuously demands discoveries of new targets and therapies. Here, we assess the function and therapeutic value of SIRT6 in metastatic castration-resistant prostate cancer. The expression of SIRT6 was examined in prostate cancer tissue microarray by immunohistochemistry staining. The functions of SIRT6 and underlying mechanisms were elucidated by and experiments. We also developed an efficient method to silence SIRT6 by aptamer-modified exosomes carrying small interfering RNA and tested the therapeutic effect in the xenograft mice models. SIRT6 expression is positively correlated with prostate cancer progression. Loss of SIRT6 significantly suppressed proliferation and metastasis of prostate cancer cell lines both and . SIRT6-driven prostate cancer displays activation of multiple cancer-related signaling pathways, especially the Notch pathway. Silencing SIRT6 by siRNA delivered through engineered exosomes inhibited tumor growth and metastasis. SIRT6 is identified as a driver and therapeutic target for metastatic prostate cancer in our findings, and inhibition of SIRT6 by engineered exosomes can serve as a promising therapeutic tool for clinical application.

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