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  • Aberrant USP11 expression regulates NF90 to promote proliferation and metastasis in hepatocellular carcinoma.

Aberrant USP11 expression regulates NF90 to promote proliferation and metastasis in hepatocellular carcinoma.

American journal of cancer research (2020-06-09)
Changmao Zhang, Chengrong Xie, Xiaomin Wang, Yayu Huang, Shaoyang Gao, Jing Lu, Yuyan Lu, Sheng Zhang
RESUMO

Growing evidence indicates that deubiquitinase ubiquitin-specific protease 11 (USP11) plays an important role in cellular function by regulating the stability of its substrates. USP11 is dysregulated in many types of cancer and involved in tumor development and progression. We previously showed that USP11 was upregulated in hepatocellular carcinoma (HCC) and promoted HCC cell invasion and metastasis potency. However, the mechanism underlying the role of USP11 in HCC cell metastasis and its function in cell proliferation remain unknown. Here, CCK-8, soft agar assays and nude mouse models showed that USP11 was essential for HCC cells survival and proliferation in vitro and in vivo. Results form mass spectrometry, co-immunoprecipitation, and ubiquitination assays demonstrated that USP11 interacted with nuclear factor 90 (NF90) and promoted its deubiquitination, thereby stabilizing it in HCC cells. Moreover, the effect of USP11 on promoting HCC cells proliferation and metastasis was dependent on NF90, and USP11 expression was positively correlated with NF90 expression in human HCC tissues, as demonstrated via immunohistochemistry. Collectively, the present findings indicated that USP11 binded to and deubiquitinated NF90, thereby stabilizing the protein expression level and promoting HCC cell proliferation and metastasis. NF90 was identified as an important downstream target of USP11. Dysregulated signaling of this novel USP11/NF90 axis might promote HCC proliferation and metastasis, and the axis could be a potential therapeutic target in HCC.

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Millipore
Agarose de proteína G, vazão rápida, Protein G Agarose, Fast Flow suitable for medium and low pressure chromatography of IgG from mouse, sheep, and rabbit, and for immunoprecipitations.
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Ramatroban, ≥98% (HPLC), solid