Cao Jian, Du Lin, Zhao Xueheng, Liu Zhizhong, Yuan Junbin, Luo Yanwei, Zhang Shanshan, Qin Zailong, Guo Jie
Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China.
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China.
Genes Immun. 2024 Dec;25(6):447-458. doi: 10.1038/s41435-024-00295-2. Epub 2024 Sep 6.
Penile squamous cell carcinoma (PSCC) is becoming increasingly common and posing a severe threat to men's health, particularly in developing countries. The function of long non-coding RNAs (lncRNAs) in PSCC progression remains mysterious. Therefore, we explored the significance of lncRNAs in the competing endogenous RNA (ceRNA) network in PSCC tumor progression. The 5 healthy and 6 tumor tissue samples were subjected to lncRNA sequencing. Using miRcode, LncBase, miRTarBase, miRWalk, and TargetScan, we constructed a ceRNA network of differentially expressed lncRNAs, miRNAs, and mRNAs. Our analysis resulted in a ceRNA network consisting of 4 lncRNAs, 18 miRNAs, and 38 mRNAs, whose upstream regulators, the lncRNAs MIR205HG, MIAT, HCP5, and PVT1, were all elevated in PSCC. Immunohistochemical staining confirmed that cell proliferation-related genes TFAP2C, MKI67, and TP63, positively regulated by 4 lncRNAs, were considerably overexpressed in tumor tissues. Immune analysis revealed a significant upregulation in macrophage and exhausted T cell infiltration in PSCC. Our study identified a lncRNA-miRNA-mRNA ceRNA network for PSCC, revealing possible molecular mechanisms involved in the regulation of PSCC progression by key lncRNAs and their connections to the immunosuppressive tumor microenvironment. The ceRNA network provides a novel perspective for elucidating the pathogenesis of PSCC.
阴茎鳞状细胞癌（PSCC）正变得越来越常见，对男性健康构成严重威胁，尤其是在发展中国家。长链非编码RNA（lncRNA）在PSCC进展中的功能仍然不明。因此，我们探讨了lncRNA在PSCC肿瘤进展的竞争性内源RNA（ceRNA）网络中的意义。对5份健康组织样本和6份肿瘤组织样本进行lncRNA测序。使用miRcode、LncBase、miRTarBase、miRWalk和TargetScan，我们构建了差异表达的lncRNA、miRNA和mRNA的ceRNA网络。我们的分析得出一个由4个lncRNA、18个miRNA和38个mRNA组成的ceRNA网络，其上游调节因子lncRNA MIR205HG、MIAT、HCP5和PVT1在PSCC中均上调。免疫组织化学染色证实，受4个lncRNA正向调控的细胞增殖相关基因TFAP2C、MKI67和TP63在肿瘤组织中明显过表达。免疫分析显示PSCC中巨噬细胞和耗竭T细胞浸润显著上调。我们的研究确定了PSCC的一个lncRNA-miRNA-mRNA ceRNA网络，揭示了关键lncRNA调控PSCC进展的可能分子机制及其与免疫抑制性肿瘤微环境的联系。该ceRNA网络为阐明PSCC的发病机制提供了新的视角。
