Lee Jin-Kwon, Lee Seung-Jun, Hah Young-Sool, Ji Yeong-Ho, Ju Young-Tae, Lee Young-Joon, Jeong Chi-Young, Kim Ju-Yeon, Park Ji-Ho, Kim Jae-Myung, Cho Jin-Kyu, Kim Han-Gil, Kwag Seung-Jin
Department of Surgery, Gyeongsang National University Changwon Hospital, Changwon, Korea.
Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Korea.
Ann Surg Treat Res. 2023 Dec;105(6):385-395. doi: 10.4174/astr.2023.105.6.385. Epub 2023 Nov 29.
This study aimed to investigate the potential role of copine-1 (CPNE1), a calcium-dependent membrane-binding protein encoded by the gene, in colorectal cancer (CRC). Despite previous research on the involvement of copine family members in various solid tumors, the specific role of CPNE1 in CRC remains poorly understood.
We conducted clinicopathological analysis and functional studies to explore the impact of CPNE1 in human CRC. We examined the expression levels of CPNE1 in CRC patients and correlated it with invasive depth, lymph node metastasis, distant metastasis, lymphatic invasion, and TNM stage. Additionally, we performed experiments to assess the functional consequences of CPNE1 knockdown in CRC cells, including proliferation, colony formation, migration, invasion, and the expression of key regulators involved in the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, we evaluated the effects of CPNE1 knockdown on tumor growth using a xenograft mouse model.
High expression of CPNE1 was significantly associated with advanced tumor features in CRC patients. CPNE1 knockdown in CRC cells led to impaired abilities in proliferation, colony formation, migration, and invasion. Furthermore, CPNE1 silencing resulted in the suppression of protein expression related to the cell cycle and EMT. In the xenograft mouse model, CPNE1 knockdown inhibited tumor growth.
CPNE1 plays a crucial role in promoting tumorigenesis and metastasis in human CRC. By regulating the cell cycle and EMT, CPNE1 influences critical cellular processes at the membrane-cytoplasm interface. These results provide valuable insights into the potential development of novel therapeutic strategies for CRC targeting CPNE1.
本研究旨在探讨由该基因编码的钙依赖性膜结合蛋白——共五聚体蛋白1（CPNE1）在结直肠癌（CRC）中的潜在作用。尽管此前已有关于共五聚体蛋白家族成员参与各种实体瘤的研究，但CPNE1在CRC中的具体作用仍知之甚少。
我们进行了临床病理分析和功能研究，以探究CPNE1对人类CRC的影响。我们检测了CRC患者中CPNE1的表达水平，并将其与浸润深度、淋巴结转移、远处转移、淋巴管浸润和TNM分期相关联。此外，我们进行了实验，以评估CRC细胞中CPNE1基因敲低的功能后果，包括增殖、集落形成、迁移、侵袭以及参与细胞周期和上皮-间质转化（EMT）的关键调节因子的表达。此外，我们使用异种移植小鼠模型评估了CPNE1基因敲低对肿瘤生长的影响。
CPNE1的高表达与CRC患者的晚期肿瘤特征显著相关。CRC细胞中CPNE1基因敲低导致增殖、集落形成、迁移和侵袭能力受损。此外，CPNE1沉默导致与细胞周期和EMT相关的蛋白表达受到抑制。在异种移植小鼠模型中，CPNE1基因敲低抑制了肿瘤生长。
CPNE1在促进人类CRC的肿瘤发生和转移中起关键作用。通过调节细胞周期和EMT，CPNE1影响细胞膜-细胞质界面的关键细胞过程。这些结果为针对CPNE1的CRC新型治疗策略的潜在开发提供了有价值的见解。
