Fu Jixing, Zhao Jianhua, Zhang Huamin, Fan Xiaoli, Geng Wenjun, Qiao Shaohua
Department of Dermatology, Liaocheng Second People's Hospital, Shandong First Medical University Affiliated Liaocheng Second Hospital, Linqing, Shandong 252601, P.R. China.
Exp Ther Med. 2021 Feb;21(2):116. doi: 10.3892/etm.2020.9548. Epub 2020 Dec 3.
The role of microRNAs (miRNAs/miRs) in governing the progression of cutaneous squamous cell carcinoma (cSCC) has been the focus of recent studies. However, the functional role of miR-451a in cSCC growth remains poorly understood. Therefore, the present study aimed to determine the expression levels of miR-451a in cSCC cell lines and the involvement of miR-451a in cSCC progression. The results revealed that the expression levels of miR-451a were downregulated in cSCC tissues and cell lines, and that this subsequently upregulated 3-phosphoinositide-dependent protein kinase-1 (PDPK1) expression levels. PDPK1 was validated as a direct target of miR-451a in cSCC using bioinformatics software Starbase, dual-luciferase reporter gene assays and western blotting. Additionally, CCK-8, EdU and Transwell assays, as well as flow cytometry and Hoechst 3325 staining, were performed to assess the malignant aggressiveness of cSCC cells. Overexpression of miR-451a was demonstrated to impair the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and promoted apoptosis in cSCC cells by interacting with PDPK1, possibly by direct targeting. Furthermore, the western blotting results indicated that miR-451a overexpression may block the PI3K/AKT signaling pathway by interacting with PDPK1. In conclusion, the findings of the present study suggested that miR-451a may prevent the proliferation, migration, invasion and EMT of cSCC cells through the PDPK1-mediated PI3K/AKT signaling pathway, which may offer potential therapeutic targets for the treatment of cSCC.
微小RNA（miRNA/miR）在皮肤鳞状细胞癌（cSCC）进展过程中的作用一直是近期研究的重点。然而，miR-451a在cSCC生长中的功能作用仍知之甚少。因此，本研究旨在确定miR-451a在cSCC细胞系中的表达水平以及miR-451a在cSCC进展中的作用。结果显示，miR-451a在cSCC组织和细胞系中的表达水平下调，随后上调了3-磷酸肌醇依赖性蛋白激酶-1（PDPK1）的表达水平。使用生物信息学软件Starbase、双荧光素酶报告基因检测和蛋白质印迹法验证了PDPK1是cSCC中miR-451a的直接靶点。此外，进行了CCK-8、EdU和Transwell检测，以及流式细胞术和Hoechst 3325染色，以评估cSCC细胞的恶性侵袭性。结果表明，miR-451a的过表达通过与PDPK1相互作用，可能是直接靶向作用，损害了cSCC细胞的增殖、迁移、侵袭和上皮-间质转化（EMT），并促进了细胞凋亡。此外，蛋白质印迹结果表明，miR-451a的过表达可能通过与PDPK1相互作用阻断PI3K/AKT信号通路。总之，本研究结果表明，miR-451a可能通过PDPK1介导的PI3K/AKT信号通路阻止cSCC细胞的增殖、迁移、侵袭和EMT，这可能为cSCC的治疗提供潜在的治疗靶点。
