CREC Family Genes as Biomarkers and Therapeutic Targets in Lung Adenocarcinoma: In vitro and In silico Insights.

IF 2.3 4区 医学 Q3 ONCOLOGY
Yimin Jiang, Guangfu Zhu, Xueqin Cheng, Xinyue Mo, Yi Chen, Fengqi Xu, MeiFang Wang, Yijun Tang
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引用次数: 0

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC), characterized by poor prognosis and limited treatment options.

Material and methods: This study investigated the expression patterns and functional roles of the CREC family genes (RCN1, RCN2, RCN3, SDF2, and CALU) in LUAD using vari-ous detailed molecular and in silico experiments.

Results: RT-qPCR analysis revealed significant upregulation of all five genes in LUAD cell lines compared to normal controls, with ROC curve analysis suggesting their potential as di-agnostic biomarkers. Validation using independent datasets (Oncomine, UALCAN, and HPA) confirmed these findings at both the transcript and protein levels. Stage-specific ex-pression and promoter methylation analyses demonstrated that RCN1 and CALU exhibit higher expression in advanced stages, while promoter hypomethylation correlated with gene overexpression in LUAD. Mutation and copy number variation (CNV) analyses indicated that CREC gene alterations are common in LUAD, with CALU and RCN3 frequently mu-tated. Functional assays revealed that knockdown of SDF2 and CALU significantly reduced cell proliferation, colony formation, and wound healing abilities in A549 cells, suggesting their roles in promoting LUAD progression. Gene enrichment and miRNA interaction anal-yses highlighted the involvement of CREC genes in processes like calcium binding, oxida-tive stress response, and immune regulation. CALU emerged as a potential prognostic mark-er, showing a significant association with poorer survival outcomes.

Conclusion: Together, the findings of this study suggested that CREC family genes may serve as promising diagnostic and therapeutic targets in LUAD.

CREC家族基因作为肺腺癌的生物标志物和治疗靶点:体外和计算机观察。
背景:肺腺癌(LUAD)是非小细胞肺癌(NSCLC)中最常见的亚型,其特点是预后差,治疗选择有限。材料和方法:本研究通过各种详细的分子和计算机实验研究了CREC家族基因(RCN1、RCN2、RCN3、SDF2和CALU)在LUAD中的表达模式和功能作用。结果:RT-qPCR分析显示,与正常对照相比,LUAD细胞系中所有5个基因的表达均显著上调,ROC曲线分析表明它们有可能作为诊断性生物标志物。使用独立数据集(Oncomine, UALCAN和HPA)验证在转录物和蛋白质水平上证实了这些发现。阶段特异性表达和启动子甲基化分析表明,RCN1和CALU在晚期表现出更高的表达,而启动子低甲基化与LUAD中基因过表达相关。突变和拷贝数变异(CNV)分析表明,CREC基因改变在LUAD中很常见,CALU和RCN3经常发生突变。功能分析显示,敲低SDF2和CALU可显著降低A549细胞的细胞增殖、集落形成和伤口愈合能力,提示它们在促进LUAD进展中的作用。基因富集和miRNA相互作用分析强调了CREC基因参与钙结合、氧化应激反应和免疫调节等过程。CALU作为一种潜在的预后指标,显示出与较差的生存结果显著相关。结论:本研究结果表明,CREC家族基因可能是LUAD有希望的诊断和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current cancer drug targets
Current cancer drug targets 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
105
审稿时长
1 months
期刊介绍: Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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