已经表明RNA解旋酶DHX33在各种人类癌症中异常表达，然而，其在肿瘤发生中的作用尚未完全理解。在本报告中，我们发现一类DNA结构蛋白，HMGBs，可以通过DHX33在癌细胞中调控，而在正常细胞中无法达到调控作用。具体而言，DHX33敲除导致HMGBs基因转录和蛋白表达的下调。值得注意的是，在RAS驱动的肺癌发生中，核HMGBs蛋白可以通过DHX33诱导表达。当DHX33被敲除时，HMGBs的过表达被削弱。机制上，我们发现DHX33能够结合到HMGB家族基因的启动子上，并通过基因启动子上的去甲基化调节它们的转录。我们的研究揭示了一个DHX33促进肿瘤发生的新机制，并强调了其在人类癌症治疗中的价值。© 2023 Elsevier Inc. 版权所有。

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.Copyright © 2023 Elsevier Inc. All rights reserved.