Department of Hepatopancreatobiliary Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Huansha Road, NO.261, Hangzhou, 310006, China.
Zhejiang Provincial Research Center for Diagnosis and Treatment of Heapatobiliary Diseases, Hangzhou, China.
J Cancer Res Clin Oncol. 2023 Jul;149(7):3023-3031. doi: 10.1007/s00432-022-04146-3. Epub 2022 Jul 19.
Recent studies have demonstrated that kinetochore-associated protein 1 (KNTC1) plays a significant role in the carcinogenesis of numerous types of cancer. This study aimed to explore the role and possible mechanisms of KNTC1 in the development of pancreatic cancer.
We analyzed differentially expressed genes by RNA sequencing in three paired pancreatic cancer and para-cancerous tissue samples and found that the expression of KNTC1 was significantly upregulated in pancreatic cancer. A Cancer and Tumor Gene Map pan-analysis showed that high expression of KNTC1 was related to poor prognosis in 9499 tumor samples. With immunohistochemical staining, we found that the high expression of KNTC1 in pancreatic cancer was related to pathological grade and clinical prognosis. Similarly, RT-PCR results indicated that the expression of KNTC1 was higher in three groups of pancreatic cancer cell lines (BxPC-3, PANC-1, and SW1990) than in normal pancreatic ductal cells. We introduced lentivirus-mediated shRNA targeting KNTC1 into PANC-1 and SW1990 cells and found that KNTC1 knockdown significantly decreased cell growth and increased cell apoptosis compared to the control group cells. Bioinformatic analysis of the cell expression profile revealed that differential genes were mainly enriched in the cell cycle, mitosis, and STAT3 signaling pathways, and co-immunoprecipitation confirmed an interaction between KNTC1 and cell division cycle associated 8.
KNTC1 could be linked to the pathophysiology of pancreatic cancer and may be an early diagnostic marker of cervical precancerous lesions.
最近的研究表明，着丝粒相关蛋白 1（KNTC1）在多种癌症的发生中起着重要作用。本研究旨在探讨 KNTC1 在胰腺癌发展中的作用和可能的机制。
我们通过对三对配对的胰腺癌和癌旁组织样本进行 RNA 测序分析，发现 KNTC1 的表达在胰腺癌中显著上调。癌症和肿瘤基因图谱泛分析显示，KNTC1 的高表达与 9499 个肿瘤样本的不良预后相关。通过免疫组织化学染色，我们发现胰腺癌中 KNTC1 的高表达与病理分级和临床预后相关。同样，RT-PCR 结果表明，在三组胰腺癌细胞系（BxPC-3、PANC-1 和 SW1990）中的表达高于正常胰腺导管细胞。我们将靶向 KNTC1 的慢病毒介导 shRNA 引入 PANC-1 和 SW1990 细胞，发现与对照组细胞相比，KNTC1 敲低显著降低了细胞生长并增加了细胞凋亡。细胞表达谱的生物信息学分析表明，差异基因主要富集在细胞周期、有丝分裂和 STAT3 信号通路中，共免疫沉淀证实了 KNTC1 与细胞分裂周期相关蛋白 8 的相互作用。
KNTC1 可能与胰腺癌的病理生理学有关，并且可能是宫颈癌前病变的早期诊断标志物。
