Huang Xiaoyue, Jiang Lingyu, Wen Zhaoke, Yuan Mingqing, Zhong Yonglong
Medical College, Guangxi University, Nanning 530021, PR China.
Department of Thoracic Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, PR China.
Heliyon. 2022 Oct 27;8(11):e11254. doi: 10.1016/j.heliyon.2022.e11254. eCollection 2022 Nov.
Lung adenocarcinoma (LUAD) is one of the most commonly diagnosed subtypes of lung cancer, and one of the deadliest cancers. Tetratricopeptide repeat domain 9A (TTC9) is upregulated and has played an oncogenic role in some malignant tumors. However, the expression and role of TTC9 has not yet been elucidated in LUAD. Here, we investigated the expression profiles, biological functions and potential molecular mechanism of the TTC9 gene in LUAD. TTC9 expression was significantly overexpressed in LUAD tissues compared with that in normal lung tissues. TTC9 expression was closely correlated with gender, lymph node metastasis, and survival status in the TCGA-LUAD cohort. Subsequent cellular function assays demonstrated that knockdown of TTC9 promoted PC9 cell apoptosis and inhibited cell proliferation, migration and invasion, leading to cell cycle arrest in G2 phase. Moreover, inhibition of TTC9 suppressed the tumorigenicity of PC9 cells in nude mice. TTC9 might serve as oncogene in LUAD through cancer-related signaling pathways including p38 MAPK pathway. The expression of TTC9 gene might be modulated by DNA copy number variant and DNA methylation. TTC9 was significantly associated with tumor immune infiltration patterns. Accordingly, TTC9 may be a novel therapeutic target for the treatment of LUAD.
肺腺癌（LUAD）是最常见的肺癌诊断亚型之一，也是最致命的癌症之一。四肽重复结构域9A（TTC9）在一些恶性肿瘤中上调并发挥致癌作用。然而，TTC9在LUAD中的表达和作用尚未阐明。在此，我们研究了TTC9基因在LUAD中的表达谱、生物学功能及潜在分子机制。与正常肺组织相比，TTC9在LUAD组织中显著过表达。在TCGA-LUAD队列中，TTC9表达与性别、淋巴结转移及生存状态密切相关。随后的细胞功能实验表明，敲低TTC9可促进PC9细胞凋亡，抑制细胞增殖、迁移和侵袭，导致细胞周期阻滞于G2期。此外，抑制TTC9可抑制PC9细胞在裸鼠中的致瘤性。TTC9可能通过包括p38丝裂原活化蛋白激酶（MAPK）途径在内的癌症相关信号通路在LUAD中充当癌基因。TTC9基因的表达可能受DNA拷贝数变异和DNA甲基化调控。TTC9与肿瘤免疫浸润模式显著相关。因此，TTC9可能是治疗LUAD的一个新的治疗靶点。
