Exploring the regulatory mechanism of CCNA2 in colorectal cancer: insights from multiomics and experimental analysis.

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2025-05-08 DOI:10.1016/j.jbc.2025.110216

Xinyi Lei,Lanying Qiu,Qiang Chen,Lan Liao,Pengfei Yu,Wenjie Wu,Zhengyang Zhu,Chunying Li,Gang Lin,Zirui Zhuang,Yuxin Meng,Yan Wang,Cunchuan Wang,Yian Du

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引用次数: 0

Abstract

Colorectal cancer (CRC) is the third-most common cancer and the second-leading cause of mortality due to cancer worldwide. The underlying regulatory mechanism of CCNA2 in CRC was explored through multiomics and experimental analyses, thus facilitating diagnosis, therapy and prognosis. Two gene expression datasets (i.e., GSE9348 and GSE110223) were extracted from GEO. Differentially expressed genes (DEGs) were identified via GEO2R, which were used for enrichment analyses through DAVID. PPI network of DEGs was constructed by STRING, and the core genes were identified. CCNA2, a prognostic core gene for CRC, was validated in TCGA and HPA via transcriptomics and proteomics. ROC analysis was performed to evaluate the diagnostic value of CCNA2 in CRC. The therapeutic value of CCNA2 was evaluated in DGIdb through pharmacogenomics. The correlation between CCNA2 and immune infiltration was determined in TIMER by immunomics. TF-mRNA and miRNA-mRNA networks for CCNA2 were constructed in miRnet and miRDB via transcriptomics. The role and mechanism of CCNA2 in CRC were investigated both in vitro and in vivo. The miR-548x-3p/CCNA2 regulatory axis in CRC was investigated in vitro. CCNA2 showed excellent diagnostic, therapeutic, and prognostic value in CRC. CCNA2 was closely associated with tumor-infiltrating immunocytes, TFs, and miRNAs. The upregulation of CCNA2 was observed in CRC, and the knockdown of CCNA2 inhibited the proliferation, migration, and invasion while inducing apoptosis of CRC cells. The knockdown of CCNA2 could inhibit epithelial-mesenchymal transition (EMT) pathway. CCNA2 acted as a target of miR-548x-3p in regulating the biological behavior of CRC cells via the EMT-signaling pathway. CCNA2 is a potential biomarker for the diagnosis, treatment, and prognosis of CRC and is associated with immune infiltration, TF, and miRNA. The miR-548x-3p/CCNA2 axis plays a pivotal role in regulating the tumorigenesis of CRC through the EMT-signaling pathway.

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探讨CCNA2在结直肠癌中的调控机制：来自多组学和实验分析的见解。

结直肠癌（CRC）是全球第三大常见癌症和第二大癌症死亡原因。通过多组学和实验分析，探索CCNA2在CRC中的潜在调控机制，从而为CRC的诊断、治疗和预后提供依据。从GEO中提取两个基因表达数据集GSE9348和GSE110223。通过GEO2R鉴定差异表达基因（DEGs），并通过DAVID进行富集分析。利用STRING构建了DEGs的PPI网络，并鉴定了核心基因。CCNA2是CRC的预后核心基因，通过转录组学和蛋白质组学在TCGA和HPA中得到验证。采用ROC分析评价CCNA2在结直肠癌中的诊断价值。通过药物基因组学评估CCNA2在DGIdb中的治疗价值。采用免疫组学方法检测CCNA2与TIMER免疫浸润的相关性。通过转录组学在miRnet和miRDB中构建了CCNA2的TF-mRNA和miRNA-mRNA网络。在体外和体内研究了CCNA2在结直肠癌中的作用和机制。我们在体外研究了CRC中miR-548x-3p/CCNA2调控轴。CCNA2在结直肠癌中具有良好的诊断、治疗和预后价值。CCNA2与肿瘤浸润性免疫细胞、tf和mirna密切相关。CCNA2在结直肠癌中表达上调，下调CCNA2可抑制结直肠癌细胞的增殖、迁移和侵袭，同时诱导结直肠癌细胞凋亡。下调CCNA2可抑制上皮-间质转化（epithelial-mesenchymal transition， EMT）通路。CCNA2作为miR-548x-3p的靶点，通过emt信号通路调节CRC细胞的生物学行为。CCNA2是CRC诊断、治疗和预后的潜在生物标志物，与免疫浸润、TF和miRNA相关。miR-548x-3p/CCNA2轴通过emt信号通路在CRC的肿瘤发生调节中起关键作用。

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

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

期刊介绍： The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.