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


ABSTRACT: 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 TNF?-induced NF-?B activation and overexpression of ABIN-2 alleviated USP35-loss induced activation of NF-?B. Collectively, our data indicated that miR let-7a-regulated USP35 can inhibit NF-?B 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.

SUBMITTER: Liu C 

PROVIDER: S-EPMC4695033 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Liu Chunyan C   Wang Lina L   Chen Weiwen W   Zhao Shihu S   Yin Chunli C   Lin Yani Y   Jiang Anli A   Zhang Pengju P  

Oncotarget 20150901 29


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-cancer  ...[more]

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