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DDX3 在结直肠癌中充当肿瘤抑制因子，因为晚期癌症中 DDX3 的缺失通过激活 MAPK 通路促进肿瘤进展。

DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway.

机构信息

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.

Department of Kidney Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.

出版信息

Int J Biol Sci. 2022 Jun 6;18(10):3918-3933. doi: 10.7150/ijbs.73491. eCollection 2022.

DOI:10.7150/ijbs.73491
PMID:35844798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9274493/
Abstract

The treatment and prognosis of patients with advanced colorectal cancer (CRC) remain a difficult problem. Herein, we investigated the role of DEAD (Asp-Glu-Ala-Asp) box helicase 3 (DDX3) in CRC and proposed potential therapeutic targets for advanced CRC. The expression of DDX3 in CRC and its effect on prognosis were explored by databases and CRC tissue microarrays. Stable DDX3 knockdown and overexpression cell lines were established with lentiviral vectors. The effects of DDX3 on CRC were investigated by functional experiments and . The molecular mechanism of DDX3 in CRC was explored by western blotting. Molecular-specific inhibitors were further used to explore potential therapeutic targets for advanced CRC. The expression of DDX3 was decreased in advanced CRC, and patients with low DDX3 expression had a poor prognosis. and experiments showed that low DDX3 expression promoted the proliferation, migration and invasion of CRC. DDX3 loss regulated E-cadherin and β-catenin signaling through the mitogen-activated protein kinase (MAPK) pathway as shown by western blotting. In addition, the MEK inhibitor, PD98059, significantly reduced the increased cell proliferation, migration and invasion caused by knockdown of DDX3. DDX3 acts as a tumor suppressor gene in CRC. DDX3 loss in advanced cancer promotes cancer progression by regulating E-cadherin and β-catenin signaling through the MAPK pathway, and targeting the MAPK pathway may be a therapeutic approach for advanced CRC.

摘要

晚期结直肠癌（CRC）患者的治疗和预后仍然是一个难题。在此，我们研究了 DEAD（Asp-Glu-Ala-Asp）盒解旋酶 3（DDX3）在 CRC 中的作用，并提出了晚期 CRC 的潜在治疗靶点。通过数据库和 CRC 组织微阵列探讨了 DDX3 在 CRC 中的表达及其对预后的影响。利用慢病毒载体建立了稳定的 DDX3 敲低和过表达细胞系。通过功能实验和实验研究了 DDX3 对 CRC 的影响。通过 Western blot 探讨了 DDX3 在 CRC 中的分子机制。进一步使用分子特异性抑制剂来探讨晚期 CRC 的潜在治疗靶点。DDX3 在晚期 CRC 中的表达降低，DDX3 低表达的患者预后不良。和实验表明，DDX3 低表达促进 CRC 的增殖、迁移和侵袭。Western blot 显示，DDX3 缺失通过丝裂原活化蛋白激酶（MAPK）通路调节 E-钙粘蛋白和β-连环蛋白信号。此外，MEK 抑制剂 PD98059 显著降低了 DDX3 敲低引起的细胞增殖、迁移和侵袭的增加。DDX3 作为 CRC 中的肿瘤抑制基因。晚期癌症中 DDX3 的缺失通过 MAPK 通路调节 E-钙粘蛋白和β-连环蛋白信号来促进癌症进展，靶向 MAPK 通路可能是治疗晚期 CRC 的一种方法。

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