Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways.
Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways.
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DOI：
10.3389/fonc.2021.650165
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发表时间：
2021
影响因子：
4.7
通讯作者：
Jia J
中科院分区：
文献类型：
--
作者：
Gao L;Zhu D;Wang Q;Bao Z;Yin S;Qiang H;Wieland H;Zhang J;Teichmann A;Jia J
泛素特异性蛋白酶7 （USP7）作为一种去泛素化酶，通过多种机制在肿瘤进展中发挥重要作用，是潜在的治疗靶点。然而，USP7在黑色素瘤中的功能作用仍然难以捉摸。在这里，我们通过组织芯片发现USP7在人类黑色素瘤中过表达。我们采用基于tmt的定量蛋白质组学分析来评估USP7 siRNA处理的A375人黑色素瘤细胞。我们的数据揭示了受USP7影响的特定蛋白质以及多种途径和过程。我们发现磷脂酰肌醇-3激酶/Akt （PI3K-Akt）、叉头盒O （FOXO）和amp活化蛋白激酶（AMPK）信号通路可能与黑色素瘤中USP7的表达密切相关。此外，在A375细胞中敲除USP7，特别是使用CRISPR-Cas9敲除USP7，证实了USP7在体内和体外调节细胞增殖。结果表明，抑制USP7可增加AMPK β (PRKAB1)、caspase 7（CASP7）和蛋白磷酸酶2亚基B R3亚型（PPP2R3A）的表达，而降低液泡atp酶C亚基（ATP6V0C）和过氧化物酶体生物发生因子11 β (PEX11B)的表达。综上所述，这些发现揭示了USP7在通过PI3K/Akt/FOXO和AMPK信号通路调节黑色素瘤进展中的重要作用，并暗示USP7是黑色素瘤的一个有吸引力的抗癌靶点。
The ubiquitin-specific protease 7 (USP7), as a deubiquitinating enzyme, plays an important role in tumor progression by various mechanisms and serves as a potential therapeutic target. However, the functional role of USP7 in melanoma remains elusive. Here, we found that USP7 is overexpressed in human melanoma by tissue microarray. We performed TMT-based quantitative proteomic analysis to evaluate the A375 human melanoma cells treated with siRNA of USP7. Our data revealed specific proteins as well as multiple pathways and processes that are impacted by USP7. We found that the phosphatidylinositol-3-kinases/Akt (PI3K-Akt), forkhead box O (FOXO), and AMP-activated protein kinase (AMPK) signaling pathways may be closely related to USP7 expression in melanoma. Moreover, knockdown of USP7 in A375 cells, particularly USP7 knockout using CRISPR-Cas9, verified that USP7 regulates cell proliferation in vivo and in vitro. The results showed that inhibition of USP7 increases expression of the AMPK beta (PRKAB1), caspase 7(CASP7), and protein phosphatase 2 subunit B R3 isoform (PPP2R3A), while attenuating expression of C subunit of vacuolar ATPase (ATP6V0C), and peroxisomal biogenesis factor 11 beta (PEX11B). In summary, these findings reveal an important role of USP7 in regulating melanoma progression via PI3K/Akt/FOXO and AMPK signaling pathways and implicate USP7 as an attractive anticancer target for melanoma.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
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作者：
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影响因子：
32.4
作者：
van Loosdregt J;Fleskens V;Fu J;Brenkman AB;Bekker CP;Pals CE;Meerding J;Berkers CR;Barbi J;Gröne A;Sijts AJ;Maurice MM;Kalkhoven E;Prakken BJ;Ovaa H;Pan F;Zaiss DM;Coffer PJ
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Coffer PJ
影响因子：
82.9
作者：
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