Using VBIM Technique to Discover ARMC4/ODAD2 as a Novel Negative Regulator of NF-κB and a New Tumor Suppressor in Colorectal Cancer.
Using VBIM Technique to Discover ARMC4/ODAD2 as a Novel Negative Regulator of NF-κB and a New Tumor Suppressor in Colorectal Cancer.
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DOI：
10.3390/ijms23052732
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发表时间：
2022-03-01
影响因子：
5.6
通讯作者：
Lu T
中科院分区：
文献类型：
--
作者：
Martin M;Mundade R;Hartley AV;Jiang G;Jin J;Sun S;Safa A;Sandusky G;Liu Y;Lu T
由于核因子（NF）κB在炎症和癌症中起着关键作用，因此了解其调节对疾病治疗具有很大的希望。利用我们建立的基于验证的插入突变（VBIM）技术，我们发现了一种新的NF-κB负调控蛋白ARMC 4/OPAD 2，该蛋白是一种迄今为止研究较少的蛋白质。ARMC 4的高表达下调了NF-κ B依赖性基因的表达，显著降低了NF-κB活性、细胞增殖、锚定非依赖性生长和体外迁移能力，并显著降低了体内异种移植瘤的生长。免疫共沉淀实验证明ARMC 4与NF-κB形成复合物。重要的是，ARMC 4在患者肿瘤中的表达低于正常组织，表明其在CRC中具有潜在的肿瘤抑制功能。总的来说，我们通过将其鉴定为新型NF-κB负调控因子，揭示了ARMC 4功能的一个全新方面，从而揭示了ARMC 4作为CRC潜在的新治疗靶点。
Since nuclear factor (NF) κB plays pivotal roles in inflammation and cancer, understanding its regulation holds great promise for disease therapy. Using the powerful validation-based insertional mutagenesis (VBIM) technique established by us previously, we discovered armadillo repeat-containing protein 4 (ARMC4)/outer dynein arm docking complex subunit 2 (ODAD2), a rarely studied protein known to date, as a novel negative regulator of NF-κB in colorectal cancer (CRC). High expression of ARMC4 downregulated the expression of NF-κB-dependent genes, dramatically reduced NF-κB activity, cellular proliferation, anchorage-independent growth, and migratory ability in vitro, and significantly decreased xenograft tumor growth in vivo. Co-immunoprecipitation experiments demonstrated that ARMC4 forms a complex with NF-κB. Importantly, the lower ARMC4 expression in patient tumors than normal tissues indicates its potential tumor suppressor function in CRC. Collectively, we uncovered a completely new facet of ARMC4 function by identifying it as a novel NF-κB negative regulator, thus uncovering ARMC4 as a potential new therapeutic target in CRC.
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影响因子：
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作者：
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