Hao Renshan, Zhang Ye, Zhu Qi, Tan Pufang
Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Laboratory of Medicine, Baoshan Branch, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Int J Genomics. 2025 Aug 23;2025:4528082. doi: 10.1155/ijog/4528082. eCollection 2025.
Colon adenocarcinoma (COAD) is a common digestive malignancy with limited therapies and a poor prognosis. Previous studies have highlighted lncRNAs' key role in cancer, but the exact function of lncRNA in COAD remains unclear. In this study, we obtained COAD transcriptome data from the UCSC Xena database, screened for differentially expressed genes, and assessed the diagnostic efficacy of using the DESeq2 package. Subsequently, the high- and low-expression groups were enriched and analyzed for immune cell infiltration characteristics and correlation with using the CIBERSORT and ESTIMATE algorithms. Its impact on immunotherapy and drug sensitivity was assessed by combining TIDE with oncoPredict database. The target mRNAs were further screened by Encori platform and potential target drugs were predicted using molecular docking technology. Finally, qRT-PCR, CCK-8, wound healing, and transwell assays were used to assess the mRNA expression levels and potential biological functions of . expression level was upregulated in COAD samples, and the ROC curve showed the area under curve (AUC) value = 0.937, revealing its strong diagnostic ability. Functional enrichment analysis showed that its high expression was associated with activation of oxidative phosphorylation pathway, while low expression was enriched in apoptosis and immune-related signaling pathways. Immune infiltration analysis showed that was significantly associated with a variety of immune cell subtypes (e.g., macrophages and neutrophils) and might be involved in the remodeling of the tumor immune microenvironment. was identified as a key downstream mRNA target (AUC = 0.811), and three potential therapeutic drugs-demecolcine, piroxicam, and vorinostat-were predicted based on DSigDB screening and validated by molecular docking, with binding energies of -6.48, -7.15, and -5.39 kcal/mol, respectively. Finally, in vitro cellular assays confirmed that expression was elevated in COAD cell lines ( < 0.0001), and its knockdown significantly suppressed cell proliferation, migration, and invasion. This study highlights that is highly expressed in COAD and promotes tumor progression through multiple mechanisms, advancing research and treatment strategies for this malignancy.
结肠腺癌(COAD)是一种常见的消化系统恶性肿瘤,治疗方法有限且预后较差。先前的研究强调了长链非编码RNA(lncRNAs)在癌症中的关键作用,但lncRNA在COAD中的具体功能仍不清楚。在本研究中,我们从UCSC Xena数据库获取了COAD转录组数据,筛选差异表达基因,并使用DESeq2软件包评估其诊断效能。随后,利用CIBERSORT和ESTIMATE算法对高表达组和低表达组进行免疫细胞浸润特征富集分析及其与[具体内容缺失]的相关性分析。通过将TIDE与oncoPredict数据库相结合评估其对免疫治疗和药物敏感性的影响。通过Encori平台进一步筛选靶标mRNA,并使用分子对接技术预测潜在的靶标药物。最后,采用qRT-PCR、CCK-8、伤口愈合和Transwell实验评估[具体内容缺失]的mRNA表达水平和潜在生物学功能。[具体内容缺失]在COAD样本中的表达水平上调,ROC曲线显示曲线下面积(AUC)值 = 0.937,表明其具有较强的诊断能力。功能富集分析表明,其高表达与氧化磷酸化途径的激活相关,而低表达则富集于凋亡和免疫相关信号通路。免疫浸润分析表明,[具体内容缺失]与多种免疫细胞亚型(如巨噬细胞和中性粒细胞)显著相关,可能参与肿瘤免疫微环境的重塑。[具体内容缺失]被鉴定为关键的下游mRNA靶标(AUC = 0.811),基于DSigDB筛选预测了三种潜在治疗药物——秋水仙胺、吡罗昔康和伏立诺他,并通过分子对接进行验证,结合能分别为-6.48、-7.15和-5.39 kcal/mol。最后,体外细胞实验证实[具体内容缺失]在COAD细胞系中的表达升高(P < 0.0001),其敲低显著抑制细胞增殖、迁移和侵袭。本研究强调[具体内容缺失]在COAD中高表达,并通过多种机制促进肿瘤进展,为该恶性肿瘤的研究和治疗策略提供了新进展。