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

Oncotarget
Chunyan LiuPengju Zhang

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 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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Citations

Apr 25, 2018·Journal of Cell Science·Pawel LeznickiYogesh Kulathu
May 28, 2019·Journal of Biomedical Science·Ming-Jer YoungJan-Jong Hung
Dec 5, 2019·International Journal of Molecular Sciences·Jinyoung ParkEun Joo Song
Jul 2, 2020·OncoTargets and Therapy·Ting DaiQing Gong
Jan 31, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jun GongZhi-Gang She
Feb 17, 2018·Nature Communications·Jinyoung ParkEun Joo Song
Aug 27, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Ji ChengWenyi Wei
May 1, 2021·International Journal of Molecular Sciences·Shiyao ChenHuchen Zhou
May 2, 2021·Clinical and Translational Medicine·Zheng TangNitao Cheng

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Methods Mentioned

BETA
ubiquitination
deubiquitination
transfection
immunoprecipitation
co-immunoprecipitation assay
Assay
xenograft

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