Li Yilong, Kong Rui, Chen Hongze, Zhao Zhongjie, Li Le, Li Jiating, Hu Jisheng, Zhang Guangquan, Pan Shangha, Wang Yongwei, Wang Gang, Chen Hua, Sun Bei
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China.
Aging (Albany NY). 2019 Jul 21;11(14):5035-5057. doi: 10.18632/aging.102096.
Despite improvements in surgical procedures and comprehensive therapies, pancreatic cancer remains one of the most aggressive and deadly human malignancies. It is therefore necessary to determine which cellular mediators associate with prognosis in pancreatic cancer so as to improve the treatment of this disease. In the present study, mRNA array and immunohistochemical analyses showed that KLF5 is highly expressed in tissue samples from three short-surviving patients with pancreatic cancer. Survival analysis using data from The Cancer Genome Atlas showed that patients highly expressing KLF5 exhibited shorter overall and tumor-free survival times. Mechanistically, KLF5 promoted expression of E2F1, cyclin D1 and Rad51, while inhibiting expression of p16 in pancreatic cancer cells. Finally, flow cytometric analyses verified that KLF5 promotes G1/S progression of the cell cycle in pancreatic cancer cells. Collectively, these findings demonstrate that KLF5 is an important prognostic biomarker in pancreatic cancer patients, and they shed light on the molecular mechanism by which KLF5 stimulates cell cycle progression in pancreatic cancer.
尽管手术程序和综合治疗有所改进，但胰腺癌仍然是最具侵袭性和致命性的人类恶性肿瘤之一。因此，有必要确定哪些细胞介质与胰腺癌的预后相关，以便改善这种疾病的治疗。在本研究中，mRNA阵列和免疫组化分析表明，KLF5在三名生存期短的胰腺癌患者的组织样本中高表达。使用来自癌症基因组图谱的数据进行的生存分析表明，高表达KLF5的患者总体生存期和无瘤生存期较短。从机制上讲，KLF5促进胰腺癌细胞中E2F1、细胞周期蛋白D1和Rad51的表达，同时抑制p16的表达。最后，流式细胞术分析证实，KLF5促进胰腺癌细胞中细胞周期的G1/S期进程。总的来说，这些发现表明KLF5是胰腺癌患者重要的预后生物标志物，并且揭示了KLF5刺激胰腺癌细胞周期进程的分子机制。
