The impact of SOX4-activated CTHRC1 transcriptional activity regulating DNA damage repair on cisplatin resistance in lung adenocarcinoma

作者全名："Ai, Cheng; Huang, Zhenhao; Rong, Tenghao; Shen, Wang; Yang, Fuyu; Li, Qiang; Bi, Lei; Li, Wen"

作者地址："[Ai, Cheng; Huang, Zhenhao; Rong, Tenghao; Yang, Fuyu; Li, Qiang; Bi, Lei] Chongqing Med Univ, Bishan Hosp, Dept Cardiothorac Surg, 9 Shuangxing Ave, Chongqing 402760, Peoples R China; [Ai, Cheng] Nanjing Univ, Nanjing Drum Tower Hosp, Affiliated Hosp, Dept Thorac Surg,Med Sch, Nanjing 210008, Peoples R China; [Shen, Wang; Li, Wen] Sichuan Univ, Lung Canc Ctr, West China Hosp, 37 Guoxue Alley, Chengdu 610041, Peoples R China"

通信作者："Ai, C (通讯作者)，Chongqing Med Univ, Bishan Hosp, Dept Cardiothorac Surg, 9 Shuangxing Ave, Chongqing 402760, Peoples R China.; Li, W (通讯作者)，Sichuan Univ, Lung Canc Ctr, West China Hosp, 37 Guoxue Alley, Chengdu 610041, Peoples R China."

来源：ELECTROPHORESIS

ESI学科分类：CHEMISTRY

WOS号：WOS:001204072100001

JCR分区：Q2

影响因子：2.9

年份：2024

卷号：45

期号：15-16

开始页：1408

结束页：1417

文献类型：Article

关键词：cisplatin resistance; CTHRC1; DNA damage repair; lung adenocarcinoma; SOX4

摘要："Lung adenocarcinoma (LUAD) is the predominant subtype within the spectrum of lung malignancies. CTHRC1 has a pro-oncogenic role in various cancers. Here, we observed the upregulation of CTHRC1 in LUAD, but its role in cisplatin resistance in LUAD remains unclear. Bioinformatics analysis was employed to detect CTHRC1 and SRY-related HMG-box 4 (SOX4) expression in LUAD. Gene Set Enrichment Analysis predicted the enriched pathways related to CTHRC1. JASPAR and MotifMap databases predicted upstream transcription factors of CTHRC1. Pearson analysis was conducted to analyze the correlation between genes of interest. The interaction and binding relationship between CTHRC1 and SOX4 were validated through dual-luciferase and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction determined the expression of CTHRC1 and SOX4 genes. CCK-8 was performed to assess cell viability and calculate IC50 value. Flow cytometry examined the cell cycle. Comet assay and western blot assessed DNA damage. CTHRC1 and SOX4 were upregulated in LUAD. CTHRC1 exhibited higher expression in cisplatin-resistant A549 cells compared to cisplatin-sensitive A549 cells. Knockdown of CTHRC1 enhanced DNA damage during cisplatin treatment and increased the sensitivity of LUAD cells to cisplatin. Additionally, SOX4 modulated DNA damage repair (DDR) by activating CTHRC1 transcriptional activity, promoting cisplatin resistance in LUAD cells. SOX4 regulated DDR by activating CTHRC1, thereby enhancing cisplatin resistance in LUAD cells. The finding provides a novel approach to address clinical cisplatin resistance in LUAD, with CTHRC1 possibly serving as a candidate for targeted therapies in addressing cisplatin resistance within LUAD."

基金机构：Natural Science Foundation of Chongqing CSTC; [cstc2021jcyj-msxmX1207]

基金资助正文：The study was supported by the Natural Science Foundation of Chongqing CSTC (grant number: cstc2021jcyj-msxmX1207).