Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Cell Mol Med. 2022 Nov;26(21):5473-5485. doi: 10.1111/jcmm.17575. Epub 2022 Oct 5.
EN1 is well known as a transcription factor in other tumours, but its role in NPC is unclear. In this study, we first used bioinformatics to analyse GEO data to obtain the differentially expressed gene EN1, and subsequently verified that EN1 was highly expressed in nasopharyngeal carcinoma cells by tissue microarrays as well as cell lines. Further, we down-regulated the expression of EN1 in cells for RNA sequencing. The analysis of sequencing results using KEGG and GO revealed significant changes in cell proliferation and cycle function after downregulation of EN1. Meanwhile, we found that cells underwent senescence after inhibition of EN1 under electron microscopy and the SA-β-gal assays. Based on the sequencing results, we verified that EN1 can promote the proliferation and cycle of NPC cells in cell function experiments and animal experiments. To investigate how EN1 affects cell senescence, we found that EN1 transcriptional regulation of COL22A1 regulated cell proliferation and cycle via CDK4/6-cyclin D1-Rb signalling pathway by dual luciferase reporter, Immunoblotting and rescue experiment. Accordingly, we uncovered that EN1 could serve as a target for the regulation of senescence in NPC.
EN1 在其他肿瘤中作为转录因子广为人知,但它在 NPC 中的作用尚不清楚。在本研究中,我们首先使用生物信息学方法分析 GEO 数据以获得差异表达基因 EN1,随后通过组织微阵列和细胞系验证了 EN1 在鼻咽癌细胞中高表达。进一步,我们通过 RNA 测序下调细胞中 EN1 的表达。KEGG 和 GO 分析测序结果表明,下调 EN1 后细胞增殖和周期功能发生显著变化。同时,我们发现电子显微镜和 SA-β-gal 检测显示,EN1 抑制后细胞发生衰老。基于测序结果,我们在细胞功能实验和动物实验中验证了 EN1 可促进 NPC 细胞的增殖和周期。为了研究 EN1 如何影响细胞衰老,我们发现通过双荧光素酶报告、免疫印迹和挽救实验,EN1 对 COL22A1 的转录调控通过 CDK4/6-cyclin D1-Rb 信号通路调节细胞增殖和周期。因此,我们揭示了 EN1 可作为 NPC 中衰老调控的靶点。