The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan 653199, China.
Shenzhen KeYe Life Technologies, Co., Ltd, Shenzhen, Guangdong 518122, China; Southern University of Science and Technology, Shenzhen, China.
Cell Signal. 2023 Oct;110:110832. doi: 10.1016/j.cellsig.2023.110832. Epub 2023 Aug 4.
RNA helicase DHX33 has been shown to be aberrantly expressed in various human cancers, however, its role in tumorigenesis remains incompletely understood. In this report, we uncovered that a family of DNA architecture proteins, HMGBs, can be regulated by DHX33 in cancer cells but not in normal cells. Specifically, DHX33 knockdown caused the downregulation of HMGBs at the levels of both gene transcription and protein expression. Notably, in RAS driven lung tumorigenesis, nuclear HMGBs proteins can be induced via DHX33. When DHX33 was knocked out, HMGBs overexpression was debilitated. Mechanistically, DHX33 was found to bind to the promoters of HMGB family genes and regulated their transcription through demethylation on gene promoters. Our study reveals a novel mechanism for DHX33 to promote tumorigenesis and highlights its therapeutic value in human cancers.
DHX33 是一种 RNA 解旋酶，已被证实存在于多种人类癌症中异常表达，但其在肿瘤发生中的作用尚不完全清楚。在本报告中，我们揭示了一组 DNA 结构蛋白（HMGBs）可以被 DHX33 在癌细胞中而不是正常细胞中调控。具体来说，DHX33 敲低导致 HMGBs 在基因转录和蛋白表达水平的下调。值得注意的是，在 RAS 驱动的肺癌发生中，HMGBs 蛋白可以通过 DHX33 诱导。当 DHX33 被敲除时，HMGBs 的过表达被削弱。在机制上，发现 DHX33 可以结合 HMGB 家族基因的启动子，并通过基因启动子上的去甲基化来调节它们的转录。我们的研究揭示了 DHX33 促进肿瘤发生的新机制，并强调了其在人类癌症中的治疗价值。
