RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression
RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression
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RNA解旋酶DDX24稳定LAMB1以促进肝细胞癌进展
DOI：
10.1158/0008-5472.can-21-3748
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发表时间：
2022-09-01
期刊：
影响因子：
11.2
通讯作者：
Shan, Hong
中科院分区：
文献类型：
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作者：
Liu, Tianze;Gan, Hairun;Shan, Hong
肝细胞癌（Hepatocellular carcinoma，HCC）是最具侵袭性的恶性肿瘤之一。阐明这种疾病的潜在机制可以为治疗HCC提供新的治疗策略。在这里，我们确定了一个新的作用，死亡盒解旋酶24（DDX 24），死亡盒蛋白家族的成员，在促进肝癌的进展。DDX 24在HCC组织中显著升高，并与HCC的诊断不良相关。DDX 24的过表达促进了肝癌的迁移和增殖，而DDX 24的抑制则抑制了这两种功能。机制上，DDX 24结合层粘连蛋白亚基β 1（LAMB 1）的mRNA 618 - 624 nt，并以依赖于核仁素与DDX 24 C-末端区域之间相互作用的方式增加其稳定性。此外，调节因子X8（RFX 8）被鉴定为DDX 24启动子结合蛋白，可转录上调DDX 24表达。总之，这些发现表明RFX 8/DDX 24/LAMB 1轴促进HCC进展，为HCC提供了潜在的治疗靶点。重要性：DDX 24的肿瘤促进作用的鉴定和潜在的调控机制的阐明提供了潜在的预后指标和治疗方法，以帮助改善肝细胞癌患者的预后。[图形]。
Hepatocellular carcinoma (HCC) is one of the most aggres-sive malignancies. Elucidating the underlying mechanisms of this disease could provide new therapeutic strategies for treating HCC. Here, we identified a novel role of DEAD-box helicase 24 (DDX24), a member of the DEAD-box protein family, in promoting HCC progression. DDX24 levels were significantly elevated in HCC tissues and were associated with poor prog-nosis of HCC. Overexpression of DDX24 promoted HCC migration and proliferation in vitro and in vivo, whereas sup-pression of DDX24 inhibited both functions. Mechanistically, DDX24 bound the mRNA618-624nt of laminin subunit beta 1 (LAMB1) and increased its stability in a manner dependent upon the interaction between nucleolin and the C-terminal region of DDX24. Moreover, regulatory factor X8 (RFX8) was identified as a DDX24 promoter-binding protein that transcrip-tionally upregulated DDX24 expression. Collectively, these find-ings demonstrate that the RFX8/DDX24/LAMB1 axis promotes HCC progression, providing potential therapeutic targets for HCC. Significance: The identification of a tumor-promoting role of DDX24 and the elucidation of the underlying regulatory mechanism provide potential prognostic indicators and therapeutic approaches to help improve the outcome of patients with hepato-cellular carcinoma.[GRAPHICS].