Liu Wen-Jian, Shen Jia-Pan, Zhang Ren-Quan, Fan Xiao-Yun
Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Discov Oncol. 2025 Jan 22;16(1):78. doi: 10.1007/s12672-024-01707-5.
This study aimed to identify the genes associated with the development of lung adenocarcinoma (LUAD) and potential therapeutic targets.
Differentially expressed genes (DEGs) were identified by self-transcriptome sequencing of tumor tissues and paracancerous tissues resected during surgery and combined with The Cancer Genome Atlas (TCGA) data to screen for the genes associated with LUAD prognosis. The expression was validated at mRNA and protein levels, and the gene knockdown was used to examine the impact and underlying mechanisms on lung cancer cells.
A total of 227 DEGs were identified by transcriptome sequencing, and the 20 DEGs with the most significant differences were used for co-analysis with TCGA data. The findings suggested that KRT16 and ANXA10 might have an important role in the development of LUAD after validating the mRNA and protein expression levels at the cellular level. The knockdown of KRT16 and ANXA10 inhibited the proliferation of lung cancer cells, and the cell cycle was blocked in the G1 phase. The expression of the G1/S-phase cell cycle checkpoint-related proteins cyclin D1 and cyclin E was inhibited by KRT16 and ANXA10 knockdown, respectively. The tumor formation ability decreased after KRT16 or ANXA10 knockdown in vivo.
KRT16 and ANXA10 are potential genes regulating the development of LUAD. Also, they may be potential targets for the targeted therapy of LUAD by inhibiting the proliferation of lung cancer cells and blocking the cell cycle by affecting key protein expression levels at cell cycle checkpoints.
本研究旨在鉴定与肺腺癌（LUAD）发生发展相关的基因及潜在治疗靶点。
通过对手术切除的肿瘤组织和癌旁组织进行自身转录组测序来鉴定差异表达基因（DEGs），并结合癌症基因组图谱（TCGA）数据筛选与LUAD预后相关的基因。在mRNA和蛋白质水平验证其表达，并采用基因敲低技术检测对肺癌细胞的影响及潜在机制。
通过转录组测序共鉴定出227个DEGs，选取差异最显著的20个DEGs与TCGA数据进行联合分析。在细胞水平验证mRNA和蛋白质表达水平后发现，KRT16和ANXA10可能在LUAD发生发展中起重要作用。敲低KRT16和ANXA10可抑制肺癌细胞增殖，细胞周期阻滞于G1期。敲低KRT16和ANXA10分别抑制了G1/S期细胞周期检查点相关蛋白细胞周期蛋白D1和细胞周期蛋白E的表达。体内敲低KRT16或ANXA10后肿瘤形成能力下降。
KRT16和ANXA10是调节LUAD发生发展的潜在基因。此外，它们可能是LUAD靶向治疗的潜在靶点，通过抑制肺癌细胞增殖并影响细胞周期检查点关键蛋白表达水平来阻断细胞周期。
