DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation.
DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation.
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DIAPH3 是一种预后生物标志物，通过维持 EGFR 降解来抑制结直肠癌进展
DOI：
10.1002/cam4.4793
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发表时间：
2022-12
期刊：
影响因子：
4
通讯作者：
Zou Z
中科院分区：
文献类型：
--
作者：
Huang R;Wu C;Wen J;Yu J;Zhu H;Yu J;Zou Z
肌动蛋白细胞骨架与结直肠癌细胞的增殖和迁移过程有关。然而，目前尚不清楚如何通过肌动蛋白细胞骨架基因（ACG）在CRC中实现这些调整，在这里，我们研究了枢纽预后相关ACG-Diaphanous-related α 3（DIAPH 3）在CRC中的作用，作为一个潜在的新靶点。使用来自京都基因和基因组百科全书（KEGG）的ACG基因集对CRC患者进行分组，并通过单变量和多变量考克斯回归选择预后相关的ACG，以构建预后模型。接下来，我们测试了CRC中枢纽预后相关ACG-DIAPH 3的表达，并通过shRNA构建体阐明了DIAPH 3在KM 12和SW 480中的作用。通过蛋白质印迹和免疫荧光分析EGFR的活化。结果表明，肌动蛋白细胞骨架功能是影响结直肠癌患者预后的重要因素，并与T分期、淋巴结转移等临床病理特征相关。由四种预后相关ACG构建的预后模型在1年生存期内具有中等强度（AUC = 0.71）。中心预后相关ACG DIAPH 3在CRC中下调。DIAPH 3基因的敲除可促进CRC的增殖和迁移能力。此外，DIAPH 3沉默细胞通过抑制EGFR转运至溶酶体来增加EGFR磷酸化。ACG在肿瘤侵袭中起重要作用，并有可能预测结直肠癌的预后。预后相关ACG DIAPH 3可能是一种新的预后生物标志物，DIAPH 3可以通过维持EGFR降解来抑制CRC进展。肌动蛋白细胞骨架的调节与细胞增殖和迁移过程密切相关。我们的研究表明，肌动蛋白细胞骨架基因（ACGs）在肿瘤侵袭中起重要作用，并有可能预测结直肠癌（CRC）的预后。枢纽预后相关ACG DIAPH 3可能是一种新的预后生物标志物，DIAPH 3可通过维持EGFR降解抑制CRC进展。
Actin cytoskeleton is connected with the processes of cell proliferation and migration in colorectal cancer (CRC). However, it is unknown how to accomplish these adjustments in CRC by actin cytoskeleton genes (ACGs) and here we investigated the role of hub prognosis‐related ACGs‐Diaphanous‐related formin 3 (DIAPH3) in CRC, as a potential, novel target. The ACGs gene set from the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to group CRC patients and select prognosis‐related ACGs by univariate and multivariate Cox regression for constructing prognostic model. Next, we tested hub prognosis‐related ACGs‐ DIAPH3 expression in CRC and clarified the role of DIAPH3 by shRNA constructs in KM12 and SW480. Activation of EGFR was analyzed by western blot and immunofluorescence. The results showed that actin cytoskeleton function is a significant prognostic factor for CRC patients and related to clinicopathological characteristics such as T stage and lymph node metastasis. A prognostic model constructed by four prognosis‐related ACGs has a moderate intensity to 1‐year Survival (AUC = 0.71). And hub prognosis‐related ACGs DIAPH3 is downregulated in CRC. Knockdown of DIAPH3 could promote the proliferation and migration capacity of CRC. In addition, DIAPH3‐silenced cells increase EGFR phosphorylation by inhibiting EGFR transportation to lysosome. ACGs play a significant role in tumor invasion and have the potential to predict the prognosis of CRC. Prognosis‐related ACGs DIAPH3 might be a new prognostic biomarker and DIAPH3 could inhibit CRC progression through maintaining EGFR degradation. The regulation of the actin cytoskeleton is intimately connected with the processes of cell proliferation and migration. Our study shows that actin cytoskeleton genes (ACGs) play a significant role in tumor invasion and have the potential to predict the prognosis of colorectal cancer (CRC). Hub prognosis‐related ACGs DIAPH3 might be a new prognostic biomarker and DIAPH3 could inhibit CRC progression through maintaining EGFR degradation.
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