Research Papers:

USP35 activated by miR let-7a inhibits cell proliferation and NF-κB activation through stabilization of ABIN-2

Chunyan Liu, Lina Wang, Weiwen Chen, Shihu Zhao, Chunli Yin, Yani Lin, Anli Jiang and Pengju Zhang _

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Oncotarget. 2015; 6:27891-27906. https://doi.org/10.18632/oncotarget.4451

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Chunyan Liu1, Lina Wang1, Weiwen Chen1, Shihu Zhao1, Chunli Yin1, Yani Lin1, Anli Jiang1, Pengju Zhang1

1Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, 250012, P.R. China

Correspondence to:

Pengju zhang, e-mail: zhpj@sdu.edu.cn

Keywords: ABIN-2, deubiquitylase, miR let-7a, NF-κB, USP35

Received: March 09, 2015     Accepted: June 16, 2015     Published: June 26, 2015


Ubiquitin specific protease 35 (USP35) is a member of deubiquitylases (DUBs). It remains largely unknown about the biological role and the regulation mechanism of USP35. Here, we first identified miR let-7a as a positive regulator of USP35 expression and showed that USP35 expression positively correlates with miR let-7a expression in different cancer cell lines and tissues. Then, we showed that USP35 expression was decreased dramatically in the tumor tissues compared with the adjacent non-cancerous tissues. USP35 overexpression inhibited cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, we revealed that USP35 acts as a functional DUB and stabilizes TNFAIP3 interacting protein 2 (ABIN-2) by promoting its deubiquitination. Functionally, both ABIN-2 and USP35 could inhibit TNFα-induced NF-κB activation and overexpression of ABIN-2 alleviated USP35-loss induced activation of NF-κB. Collectively, our data indicated that miR let-7a-regulated USP35 can inhibit NF-κB activation by deubiquitination and stabilization of ABIN-2 protein and eventually inhibit cell proliferation. Overall, our study provides a novel rationale of targeting miR let-7a-USP35-ABIN-2 pathway for the therapy of cancer patients.

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