Wang Yanfeng, Guo Yongxin, Song Yanping, Zou Wenbo, Zhang Junjie, Yi Qiong, Xiao Yujie, Peng Jing, Li Yingqi, Yao Lei
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Anesthesia and Operation Center, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Front Pharmacol. 2023 May 4;14:1153067. doi: 10.3389/fphar.2023.1153067. eCollection 2023.
Finding new targets is necessary for understanding tumorigenesis and developing cancer therapeutics. DExH-box helicase 9 (DHX9) plays a central role in many cellular processes but its expression pattern and prognostic value in most types of cancer remain unclear. In this study, we extracted pan-cancer data from TCGA and GEO databases to explore the prognostic and immunological role of DHX9. The expression levels of DHX9 were then verified in tumor specimens by western blot and immunohistochemistry (IHC). The oncogenic roles of DHX9 in cancers were further verified by experiments. We first verified that DHX9 is highly expressed in most tumors but significantly decreased in kidney and thyroid cancers, and it is prominently correlated with the prognosis of patients with different tumors. The phosphorylation level of DHX9 was also increased in cancers. Enrichment analysis revealed that DHX9 was involved in Spliceosome, RNA transport and mRNA surveillance pathway. Furthermore, DHX9 expression exhibited strong correlations with immune cell infiltration, immune checkpoint genes, and tumor mutational burden (TMB)/microsatellite instability (MSI). In liver, lung, breast and renal cancer cells, the knockdown or depletion of DHX9 significantly affected the proliferation, metastasis and EMT process of cancer cells. In summary, this pan-cancer investigation provides a comprehensive understanding of the prognostic and immunological role of DHX9 in human cancers, and experiments indicated that DHX9 was a potential target for cancer treatment.
寻找新的靶点对于理解肿瘤发生机制和开发癌症治疗方法至关重要。解旋酶9（DExH-box helicase 9，DHX9）在许多细胞过程中发挥核心作用，但其在大多数癌症类型中的表达模式和预后价值仍不清楚。在本研究中，我们从TCGA和GEO数据库中提取了泛癌数据，以探讨DHX9的预后和免疫作用。然后通过蛋白质免疫印迹法和免疫组织化学（IHC）在肿瘤标本中验证DHX9的表达水平。通过实验进一步验证了DHX9在癌症中的致癌作用。我们首先证实DHX9在大多数肿瘤中高表达，但在肾癌和甲状腺癌中显著降低，并且它与不同肿瘤患者的预后显著相关。DHX9的磷酸化水平在癌症中也有所增加。富集分析表明，DHX9参与剪接体、RNA转运和mRNA监测途径。此外，DHX9表达与免疫细胞浸润、免疫检查点基因以及肿瘤突变负荷（TMB）/微卫星不稳定性（MSI）表现出强烈的相关性。在肝癌、肺癌、乳腺癌和肾癌细胞中，敲低或耗尽DHX9显著影响癌细胞的增殖、转移和上皮-间质转化过程。总之，这项泛癌研究全面了解了DHX9在人类癌症中的预后和免疫作用，实验表明DHX9是癌症治疗的潜在靶点。
