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DHX33 促进 Wnt 信号下游的结肠癌发生。

DHX33 promotes colon cancer development downstream of Wnt signaling.

机构信息

Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.

Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.

出版信息

Gene. 2020 Apr 20;735:144402. doi: 10.1016/j.gene.2020.144402. Epub 2020 Jan 28.

Abstract

Colon cancer is one of the most common malignancies in the world; there is no effective therapeutic treatment after surgery. Our previous studies indicate that RNA helicase DHX33 plays a critical role in cell proliferation and cell growth. Here in this study, DHX33 is found to be highly expressed in colon cancer tissues and colon cancer cell lines. Knockdown of DHX33 significantly decreased cell proliferation and triggered apoptosis. Mechanistically, DHX33 was found to transcriptionally control multiple critical genes involved in cell cycle, apoptosis and migration. DHX33 deficiency caused decreased tumor growth for colon cancer cells in a xenograft model in vivo. With Wnt/β-cateninactivator and inhibitors, we further discovered that Wnt/β-catenin pathway regulates DHX33 transcriptionally. This study for the first time demonstratesthe important role of DHX33 in colon cancer development and reveals the underlying molecular mechanism. We also provide the initial evidence for the relationship between DHX33 and Wnt/β-catenin signaling pathway in colon cancer development.

摘要

结肠癌是世界上最常见的恶性肿瘤之一;手术后没有有效的治疗方法。我们之前的研究表明,RNA 解旋酶 DHX33 在细胞增殖和细胞生长中发挥着关键作用。在这项研究中,DHX33 被发现高表达于结肠癌组织和结肠癌细胞系中。DHX33 的敲低显著降低了细胞增殖并触发了细胞凋亡。从机制上讲,DHX33 被发现转录控制涉及细胞周期、凋亡和迁移的多个关键基因。DHX33 缺失导致异种移植模型中结肠癌细胞的肿瘤生长减少。通过 Wnt/β-catenin 激活剂和抑制剂,我们进一步发现 Wnt/β-catenin 通路转录调控 DHX33。这项研究首次证明了 DHX33 在结肠癌发生发展中的重要作用,并揭示了其潜在的分子机制。我们还为 DHX33 与结肠癌发生发展中 Wnt/β-catenin 信号通路之间的关系提供了初步证据。

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