Our previous studies have identified CA916798 as a chemotherapy resistance-associated gene in lung cancer. However, the histopathological relevance and biological function of CA916798 in lung adenocarcinoma (LUAD) remains to be delineated. In this study, we further investigated and explored the clinical and biological significance of CA916798 in LUAD. The relationship between CA916798 and clinical features of LUAD was analyzed by tissue array and online database. CCK8 and flow cytometry were used to measure cell proliferation and cell cycle of LUAD after knockdown of CA916798 gene. qRT-PCR and western blotting were used to detect the changes of cell cycle-related genes after knockdown or overexpression of CA916798. The tumorigenesis of LUAD cells was evaluated with or without engineering manipulation of CA916798 gene expression. Response to Gefitinib was evaluated using LUAD cells with forced expression or knockdown of CA916798. The analysis on LUAD samples showed that high expression of CA916798 was tightly correlated with pathological progression and poor prognosis of LUAD patients. A critical methylation site in promoter region of CA916798 gene was identified to be related with CA916798 gene expression. Forced expression of CA916798 relieved the inhibitory effects of WEE1 on CDK1 and facilitated cell cycle progression from G2 phase to M phase. However, knockdown of CA916798 enhanced WEE1 function and resulted in G2/M phase arrest. Consistently, chemical suppression of CDK1 dramatically inhibited G2/M phase transition in LUAD cells with high expression of CA916798. Finally, we found that CA916798 was highly expressed in Gefitinib-resistant LUAD cells. Exogenous expression of CA916798 was sufficient to endow Gefitinib resistance with tumor cells, but interference of CA916798 expression largely rescued response of tumor cells to Gefitinib. CA916798 played oncogenic roles and was correlated with the development of Gefitinib resistance in LUAD cells. Therefore, CA916798 could be considered as a promising prognostic marker and a therapeutic target for LUAD.

中文翻译：

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CA916798预测肺腺癌预后不良并促进吉非替尼耐药

我们之前的研究已将 CA916798 鉴定为肺癌化疗耐药相关基因。然而，CA916798 在肺腺癌 (LUAD) 中的组织病理学相关性和生物学功能仍有待阐明。在本研究中，我们进一步调查和探讨CA916798在LUAD中的临床和生物学意义。通过组织芯片和在线数据库分析CA916798与LUAD临床特征的关系。CCK8和流式细胞术用于测量CA916798基因敲低后LUAD的细胞增殖和细胞周期。qRT-PCR和western blotting用于检测CA916798敲低或过表达后细胞周期相关基因的变化。在有或没有 CA916798 基因表达的工程操作的情况下评估 LUAD 细胞的肿瘤发生。使用强制表达或敲低 CA916798 的 LUAD 细胞评估对吉非替尼的反应。对 LUAD 样本的分析表明，CA916798 的高表达与 LUAD 患者的病理进展和不良预后密切相关。CA916798基因启动子区的一个关键甲基化位点被鉴定为与CA916798基因表达相关。CA916798 的强制表达解除了 WEE1 对 CDK1 的抑制作用，并促进细胞周期从 G2 期进展到 M 期。然而，CA916798 的敲低增强了 WEE1 功能并导致 G2/M 期停滞。一致地，CDK1 的化学抑制显着抑制了 CA916798 高表达的 LUAD 细胞中的 G2/M 期转变。最后，我们发现 CA916798 在吉非替尼耐药的 LUAD 细胞中高表达。CA916798 的外源性表达足以赋予肿瘤细胞吉非替尼耐药性，但 CA916798 表达的干扰在很大程度上挽救了肿瘤细胞对吉非替尼的反应。CA916798 发挥致癌作用，并与 LUAD 细胞中吉非替尼耐药性的发展相关。因此，CA916798 可被视为 LUAD 的有前途的预后标志物和治疗靶点。