Hltf,也称为Helicase-like transcription factor,是一种重要的SWI/SNF家族蛋白,参与染色质重塑和DNA修复。Hltf的功能涉及多种生物学过程,包括基因转录、DNA损伤修复和细胞代谢等。在人类癌症中,Hltf的表达和功能常常发生改变,导致肿瘤的发生和发展。
近年来,研究表明Hltf在多种癌症中发挥重要作用。在结肠癌中,Hltf的表达受到抑制,与肿瘤的发生和发展密切相关[2]。研究发现,Hltf的表达缺失伴随着Hltf启动子区域的甲基化,导致Hltf的沉默表达。此外,Hltf的缺失还可以通过其他机制导致肿瘤的发生,例如通过调节氧化磷酸化途径和线粒体代谢[4]。在胃癌中,Hltf的甲基化也与肿瘤的发生和发展相关[1,7]。研究表明,Hltf的甲基化导致Hltf的表达下调,进而影响肿瘤的发生和发展。此外,Hltf还可以通过与其他蛋白相互作用,参与DNA损伤修复过程,维持基因组的稳定性[6]。
除了在癌症中的作用,Hltf还与DNA损伤修复和基因组稳定性密切相关。研究表明,Hltf可以与Cas9相互作用,影响CRISPR-Cas9介导的基因组编辑过程[3]。Hltf通过移除Cas9-DNA复合物,促进DNA损伤修复和基因组的稳定性。此外,Hltf还与DNA复制和细胞周期的调控相关,参与维持基因组的稳定性[5]。
综上所述,Hltf是一种重要的SWI/SNF家族蛋白,参与染色质重塑、DNA损伤修复和细胞代谢等生物学过程。Hltf在多种癌症中发挥重要作用,其表达和功能的改变与肿瘤的发生和发展密切相关。此外,Hltf还与DNA损伤修复和基因组稳定性相关,参与维持基因组的稳定性。深入研究Hltf的功能和作用机制,有助于我们更好地理解癌症的发生和发展机制,为癌症的诊断和治疗提供新的思路和策略。
参考文献:
1. Qu, Yiping, Dang, Siwen, Hou, Peng. 2013. Gene methylation in gastric cancer. In Clinica chimica acta; international journal of clinical chemistry, 424, 53-65. doi:10.1016/j.cca.2013.05.002. https://pubmed.ncbi.nlm.nih.gov/23669186/
2. Moinova, Helen R, Chen, Wei-Dong, Shen, Lanlan, Issa, Jean-Pierre, Markowitz, Sanford D. 2002. HLTF gene silencing in human colon cancer. In Proceedings of the National Academy of Sciences of the United States of America, 99, 4562-7. doi:. https://pubmed.ncbi.nlm.nih.gov/11904375/
3. Reginato, Giordano, Dello Stritto, Maria Rosaria, Wang, Yanbo, Ha, Taekjip, Cejka, Petr. 2024. HLTF disrupts Cas9-DNA post-cleavage complexes to allow DNA break processing. In Nature communications, 15, 5789. doi:10.1038/s41467-024-50080-y. https://pubmed.ncbi.nlm.nih.gov/38987539/
4. Helmer, Rebecca A, Kaur, Gurvinder, Smith, Lisa A, Chilton, Beverly S. 2019. Helicase-like transcription factor (Hltf) gene-deletion promotes oxidative phosphorylation (OXPHOS) in colorectal tumors of AOM/DSS-treated mice. In PloS one, 14, e0221751. doi:10.1371/journal.pone.0221751. https://pubmed.ncbi.nlm.nih.gov/31461471/
5. Hibi, Kenji, Nakayama, Hiroshi, Kanyama, Yasuaki, Akiyama, Seiji, Nakao, Akimasa. . Methylation pattern of HLTF gene in digestive tract cancers. In International journal of cancer, 104, 433-6. doi:. https://pubmed.ncbi.nlm.nih.gov/12584739/
6. Elserafy, Menattallah, Abugable, Arwa A, Atteya, Reham, El-Khamisy, Sherif F. 2018. Rad5, HLTF, and SHPRH: A Fresh View of an Old Story. In Trends in genetics : TIG, 34, 574-577. doi:10.1016/j.tig.2018.04.006. https://pubmed.ncbi.nlm.nih.gov/29807746/
7. Hamai, Yoichi, Oue, Naohide, Mitani, Yoshitsugu, Toge, Tetsuya, Yasui, Wataru. . DNA hypermethylation and histone hypoacetylation of the HLTF gene are associated with reduced expression in gastric carcinoma. In Cancer science, 94, 692-8. doi:. https://pubmed.ncbi.nlm.nih.gov/12901794/