Lei Xinyi, Qiu Lanying, Chen Qiang, Liao Lan, Yu Pengfei, Wu Wenjie, Zhu Zhengyang, Li Chunying, Lin Gang, Zhuang Zirui, Meng Yuxin, Wang Yan, Wang Cunchuan, Du Yian
Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Department of Chest Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
J Biol Chem. 2025 May 8;301(8):110216. doi: 10.1016/j.jbc.2025.110216.
Colorectal cancer (CRC) is the third-most common cancer and the second leading of cancer-related deaths worldwide. The underlying regulatory mechanism of cyclin A2 (CCNA2) in CRC was explored through multiomics and experimental analyses, thus facilitating diagnosis, therapy, and prognosis. GSE9348 and GSE110223 were extracted from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified via GEO2R. CCNA2, a core gene for CRC, was screened out from the protein-protein interaction network constructed by differentially expressed genes. Its diagnostic, prognostic, and therapeutic value was evaluated in Gene Expression Omnibus, The Cancer Genome Atlas, Human Protein Atlas, and Drug-Gene interaction database via transcriptomics, proteomics, and pharmacogenomics. The correlation between CCNA2 and immune infiltration was determined in Tumor Immune Estimation Resource by immunomics. Transcription factor-mRNA and miRNA-mRNA networks for CCNA2 were constructed in miRnet and miRDB via transcriptomics. The role and regulatory mechanism of CCNA2 in CRC were investigated both in vitro and in vivo. CCNA2 showed excellent diagnostic, therapeutic, and prognostic value in CRC. CCNA2 was closely associated with tumor-infiltrating immunocytes, transcription factors, and miRNAs. The knockdown of CCNA2 inhibited the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), while inducing apoptosis of CRC cells. 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. The miR-548x-3p-CCNA2 axis plays a pivotal role in regulating the tumorigenesis of CRC through the EMT-signaling pathway.
结直肠癌（CRC）是全球第三大常见癌症，也是癌症相关死亡的第二大主要原因。通过多组学和实验分析探索了细胞周期蛋白A2（CCNA2）在结直肠癌中的潜在调控机制，从而有助于诊断、治疗和预后评估。从基因表达综合数据库（Gene Expression Omnibus）中提取了GSE9348和GSE110223数据集。通过GEO2R软件鉴定差异表达基因（DEGs）。从由差异表达基因构建的蛋白质-蛋白质相互作用网络中筛选出CCNA2，它是结直肠癌的一个核心基因。通过转录组学、蛋白质组学和药物基因组学，在基因表达综合数据库、癌症基因组图谱（The Cancer Genome Atlas）、人类蛋白质图谱（Human Protein Atlas）和药物-基因相互作用数据库中评估了其诊断、预后和治疗价值。通过免疫组学在肿瘤免疫估计资源库（Tumor Immune Estimation Resource）中确定CCNA2与免疫浸润之间的相关性。通过转录组学在miRnet和miRDB中构建CCNA2的转录因子-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调控机制。CCNA2在结直肠癌中显示出优异的诊断、治疗和预后价值。CCNA2与肿瘤浸润免疫细胞、转录因子和miRNA密切相关。敲低CCNA2可抑制结直肠癌细胞的增殖、迁移、侵袭和上皮-间质转化（EMT），同时诱导细胞凋亡。CCNA2作为miR-548x-3p的靶标，通过EMT信号通路调节结直肠癌细胞的生物学行为。CCNA2是结直肠癌诊断、治疗和预后的潜在生物标志物。miR-548x-3p-CCNA2轴通过EMT信号通路在调节结直肠癌的肿瘤发生中起关键作用。
