School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Clin Exp Pharmacol Physiol. 2022 Sep;49(9):970-978. doi: 10.1111/1440-1681.13680. Epub 2022 Jun 20.
Colon adenocarcinoma (COAD) is one of the most common malignant tumours of the digestive system. Specific molecular markers play an important role in COAD diagnosis and therapy. Adenylate kinase 5 (AK5) is an enzyme that is related to energy metabolism and cancer. However, the exact role of AK5 in the progression of COAD is still unclear. In this study, the expression of AK5 in tissue samples and non-cancerous tissues of COAD patients was assessed by the bioinformatics method and western blot. Kaplan-Meier survival analysis and Cox regression analysis evaluated the prognostic significance of AK5. The biological function of AK5 in tumour progression was assessed by MTT assay, colony formation assay, transwell assay, wound healing assay, western blot and mice xenograft models. The results showed that AK5 expression in tumour tissues was lower than in non-cancerous tissues. Notably, the patients with high AK5 expression possessed a longer overall survival than the low expression patients, and low AK5 expression promoted proliferation and metastasis in COAD cells by regulating the cell-cycle pathway. Importantly, in vivo results showed that reduced AK5 expression is required for tumour growth. This study confirmed the significant role of AK5 in the development and progression of COAD. Therefore, low AK5 expression levels can be an independent prognostic biomarker, which provides new sight for the clinical diagnosis and target therapy of COAD.
结直肠腺癌（COAD）是消化系统最常见的恶性肿瘤之一。特定的分子标志物在 COAD 的诊断和治疗中起着重要作用。腺苷酸激酶 5（AK5）是一种与能量代谢和癌症相关的酶。然而，AK5 在 COAD 进展中的确切作用尚不清楚。在这项研究中，通过生物信息学方法和 Western blot 评估了 AK5 在 COAD 患者组织样本和非癌组织中的表达。Kaplan-Meier 生存分析和 Cox 回归分析评估了 AK5 的预后意义。通过 MTT 测定、集落形成测定、Transwell 测定、划痕愈合测定、Western blot 和小鼠异种移植模型评估了 AK5 在肿瘤进展中的生物学功能。结果表明，肿瘤组织中 AK5 的表达低于非癌组织。值得注意的是，高 AK5 表达的患者总生存期长于低表达的患者，低 AK5 表达通过调节细胞周期通路促进 COAD 细胞的增殖和转移。重要的是，体内结果表明，降低 AK5 表达是肿瘤生长所必需的。本研究证实了 AK5 在 COAD 发生和发展中的重要作用。因此，低 AK5 表达水平可以作为独立的预后生物标志物，为 COAD 的临床诊断和靶向治疗提供了新的视角。
