Lyu Xinran, Ding Xuchao, Ye Hui, Guo Rong, Wu Minhang, Cao Lili
Oncology Department, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.
Oncology Department, Shandong Provincial Qianfoshan Hospital, School of Medicine, Shandong University, Jinan, 250014, China.
Discov Oncol. 2022 May 16;13(1):30. doi: 10.1007/s12672-022-00494-1.
Our study aimed to determine whether Krüppel-like factor 14 (KLF14) inhibits the proliferation and promotes the apoptosis of cervical cancer cells through integrin β1 (ITGB1). Immunohistochemistry was performed to determine the expression of KLF14. The effect of KLF14 on the proliferation of cervical cancer cells was verified by Cell Counting Kit-8 (CCK-8) assays, colony formation assays and in vivo experiments. The effect of KLF14 on cervical cancer cell apoptosis was detected by flow cytometry. The targeting relationship between KLF14 and ITGB1 was evaluated by Western blotting and a dual-luciferase reporter assay. Moreover, Flow cytometry was performed to verify the relationship between KLF14 and ITGB1 on the apoptosis of cervical cancer cells. Additionally, Western blot analysis was performed to investigate the relationship between KLF14 and ITGB1 on the expression of downstream related molecules. As a result, the expression of KLF14 in cervical cancer tissues was lower than that in paracancerous tissues. KLF14 inhibited proliferation and promoted apoptosis in cervical cancer cells. Mechanistically, ITGB1 expression was significantly downregulated in KLF14-overexpressing cervical cancer cells. At the same time, we found that the effects of KLF14 and ITGB1 on apoptosis of cervical cancer cells could be mutually affected. KLF14 directly targeted ITGB1 to regulate its downstream PI3K/AKT signalling pathway. In summary, KLF14 inhibits the progression of cervical cancer by targeting ITGB1 via the PI3K/AKT signalling pathway.
我们的研究旨在确定Krüppel样因子14（KLF14）是否通过整合素β1（ITGB1）抑制宫颈癌细胞的增殖并促进其凋亡。采用免疫组织化学法检测KLF14的表达。通过细胞计数试剂盒-8（CCK-8）检测、集落形成试验和体内实验验证KLF14对宫颈癌细胞增殖的影响。采用流式细胞术检测KLF14对宫颈癌细胞凋亡的影响。通过蛋白质免疫印迹法和双荧光素酶报告基因检测评估KLF14与ITGB1之间的靶向关系。此外，采用流式细胞术验证KLF14与ITGB1在宫颈癌细胞凋亡方面的关系。另外，进行蛋白质免疫印迹分析以研究KLF14与ITGB1在下游相关分子表达方面的关系。结果显示，宫颈癌组织中KLF14的表达低于癌旁组织。KLF14抑制宫颈癌细胞的增殖并促进其凋亡。机制上，在过表达KLF14的宫颈癌细胞中，ITGB1的表达显著下调。同时，我们发现KLF14和ITGB1对宫颈癌细胞凋亡的影响可能相互作用。KLF14直接靶向ITGB1以调节其下游的PI3K/AKT信号通路。综上所述，KLF14通过PI3K/AKT信号通路靶向ITGB1抑制宫颈癌的进展。
