Wu Yue, Zhang Yijun, Lv Jian, Wang Yinzhong
General surgery department, Jiaozuo Second People's Hospital, The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, No. 17 Minzhu South Road, Liberated Area, Henan, China.
Thyroid gland breast Surgery department, Jiaozuo Second People's Hospital, The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, Henan, China.
J Bioenerg Biomembr. 2025 Sep 1. doi: 10.1007/s10863-025-10069-8.
Colorectal adenocarcinoma (COAD) poses a serious threat to the life of the patient. Notably, Uroplakin 1 A (UPK1A) is a prognostic biomarker for a variety of tumors. However, the role played by UPK1A in the occurrence and development of COAD and its associated molecular mechanisms still lacks a clear and in-depth understanding. The relationship between UPK1A expression and clinicopathological features, as well as patient prognosis, was examined through the use of online databases. Differences in UPK1A expression in COAD tissues and adjacent normal tissues were assessed in clinical samples. The effects of knocking down UPK1A under Escherichia coli (E. coli) co-culture/non-co-culture conditions on COAD cell proliferation, cell invasion, and apoptosis were investigated. In vivo subcutaneous tumor xenograft model, we knocked down the UPK1A gene in a tumor mouse model and assessed tumor growth. The effects of UPK1A and E. coli on glycolysis were investigated by detecting mRNA expression of glucose consumption, lactate production, HIF-1α, and glycolytic enzymes (GLUT1, LDHA, and PDK1). UPK1A was highly expressed in COAD tissues and showed a positive association with unfavorable outcomes in colorectal cancer patients. By knocking down UPK1A, co-culture conditions with E. coli inhibited COAD cell proliferation and invasion, promoted apoptosis, and reduced tumor growth. Knockdown of UPK1A inhibited COAD cell glycolysis by modulating HIF-1α signaling under E. coli co-culture conditions. It is suggested that UPK1A and E. coli synergistically promoted COAD cell proliferation, invasion, and tumor growth and inhibited apoptosis. By regulating HIF-1α signaling, UPK1A and E. coli were able to promote glycolysis in COAD cells. UPK1A and E. coli synergistically interfered with junctional COAD processes.
结直肠癌（COAD）对患者的生命构成严重威胁。值得注意的是，uroplakin 1 A（UPK1A）是多种肿瘤的预后生物标志物。然而，UPK1A在COAD发生发展中的作用及其相关分子机制仍缺乏清晰深入的认识。通过使用在线数据库研究了UPK1A表达与临床病理特征以及患者预后之间的关系。在临床样本中评估了COAD组织和相邻正常组织中UPK1A表达的差异。研究了在大肠杆菌（E. coli）共培养/非共培养条件下敲低UPK1A对COAD细胞增殖、细胞侵袭和凋亡的影响。在体内皮下肿瘤异种移植模型中，我们在肿瘤小鼠模型中敲低UPK1A基因并评估肿瘤生长。通过检测葡萄糖消耗、乳酸产生、HIF-1α和糖酵解酶（GLUT1、LDHA和PDK1）的mRNA表达，研究了UPK1A和大肠杆菌对糖酵解的影响。UPK1A在COAD组织中高表达，并且与结直肠癌患者的不良预后呈正相关。通过敲低UPK1A，与大肠杆菌的共培养条件抑制了COAD细胞的增殖和侵袭，促进了凋亡，并减少了肿瘤生长。在大肠杆菌共培养条件下，敲低UPK1A通过调节HIF-1α信号通路抑制了COAD细胞的糖酵解。提示UPK1A和大肠杆菌协同促进了COAD细胞的增殖、侵袭和肿瘤生长，并抑制了凋亡。通过调节HIF-1α信号通路，UPK1A和大肠杆菌能够促进COAD细胞的糖酵解。UPK1A和大肠杆菌协同干扰了结直肠癌的相关进程。
