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Abstract：
Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms remain to be further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the role and mechanisms of ALDOA in CRC are still unclear. In the current study, high expression levels and enzymatic activity of ALDOA were detected in CRC tissues and cell lines, indicating the clinical significance of ALDOA in human CRC. In addition, silencing ALDOA significantly impaired the proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, immunoprecipitation assays and mass spectrometry analysis identified the binding protein COPS6 of ALDOA. Furthermore, the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by COPS6 depletion, demonstrating COPS6 was required for ALDOA in mediating CRC progress. Moreover, the epithelial-mesenchymal transition (EMT) program and MAPK signaling pathway were found to be activated by ALDOA overexpression as well. In summary, our findings suggested that ALDOA facilitated the proliferation and metastasis of CRC by binding and regulating COPS6, inducing EMT, and activating the mitogen-activated protein kinase (MAPK) signaling pathway. The present study provided evidence for ALDOA as a promising potential biomarker for CRC.
摘要：
结直肠癌是严重威胁人类健康的疾病,其基本机制仍有待进一步探索。醛缩酶A（ALDOA）因其与多种癌症的相关性而受到越来越多的关注。但ALDOA在CRC中的作用和机制尚不清楚.在目前的研究中,在CRC组织和细胞系中检测到ALDOA的高表达水平和酶活性，表明ALDOA在人类CRC中的临床意义。此外,沉默ALDOA显著损害CRC细胞的体外和体内增殖和转移。机械上,免疫沉淀测定和质谱分析鉴定了ALDOA的结合蛋白COPS6。此外，上调ALDOA对CRC细胞增殖和转移的促进作用被COPS6耗竭抑制,证明COPS6是ALDOA介导CRC进展所必需的.此外，发现上皮-间质转化（EMT）程序和MAPK信号通路也被ALDOA过表达激活。总之,我们的研究结果表明，ALDOA通过结合和调节COPS6，诱导EMT，促进CRC的增殖和转移，激活丝裂原活化蛋白激酶(MAPK)信号通路。本研究提供了ALDOA作为CRC潜在生物标志物的证据。
