DHX36是一种具有转录调控功能的G四链体(G4)解旋酶，它能通过解旋基因中的G4结构促进基因转录。DHX36是HeLa细胞裂解液中G4解旋活性最主要的来源，其G4解旋活性远远高于其双链解旋活性。因此解旋G4被认为是DHX36的主要功能。然而，该结论并没有在体内鉴定过。此外，DHX36在大多数乳腺癌和30%的肺癌中高表达，说明DHX36对癌症的发生发展有贡献。一些研究报道DHX36能够激活癌基因，但DHX36的潜在致癌机制还缺乏全面、深入地研究。.为了探讨上述两个问题，本项目将采用先进的单碱基分辨率的新生RNA测序法，在全转录组中分析DHX36在乳腺癌细胞内的直接靶基因。在此结论的基础上进一步验证DHX36的DNA G4结合位点，并分析DHX36通过解旋G4调控了哪些癌基因的表达。通过以上研究，申请人将鉴定解旋G4是否为DHX36体内的主要功能，并阐释DHX36、G4及癌症三者的关系。

DHX36 protein is a G-quadruplex (G4) helicase, it can promote gene transcription by resolving G4 structure in genes. In this way, DHX36 is a transcriptional regulator. DHX36 is the major source of G4-DNA resolving activity in HeLa cell lysates, and its G4-resolving activity is much higher than its dsDNA-resolving activity. Therefore, resolving G4 is considered to be the main function of DHX36. However, this conclusion has not been identified in vivo. In addition, DHX36 is highly expressed in most breast cancers and 30% of lung cancers, suggesting that DHX36 contributes to the development of cancer. Some studies have reported that DHX36 can activate the transcription of oncogenes, but there still lack comprehensive and in-depth studies of the potential carcinogenic mechanisms of DHX36.. In order to study the above two issues, this project will use the base-esolution nascent-RNA sequencing technology to analyze DHX36's direct target genes in breast cancer cells at transcriptome-scale. Based on this result, we will further seek the DNA G4 binding site of DHX36 in breast cancer cells, and analyze the expression of which oncogenes in breat cancer cells is regulated by G4-resolving DHX36. Through the above research, we will identify whether resolving G4 is the main function of DHX36 in vivo, and illucidate the relationship between DHX36, G4 and cancer.