Du Lin, Lv Shanshan, Jiang Zhenzhen, Song Xiaohong, Liu Leping, Huang Rong, Nie Xinmin, Gui Rong, Li Jian, Zhang Junhua, Guo Jie, Cao Jian, Liu Zhizhong, Gong Zhaojian, Luo Yanwei
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
Int J Med Sci. 2025 Jun 12;22(12):2919-2931. doi: 10.7150/ijms.112109. eCollection 2025.
Penile squamous cell carcinoma (PSCC) is a malignant reproductive tumor, and circRNAs are essential regulators in the progression of cancers. However, their specific roles in PSCC have not been adequately investigated, which are available to function via the competing endogenous RNA (ceRNA) network. We collected 5 normal and 6 PSCC tissue samples for bulk RNA sequencing and obtained differentially expressed circRNAs (DE-circRNAs) and differentially expressed mRNAs (DE-mRNAs). Then we conducted a correlation analysis between them, followed by the prediction and intersection of their target miRNAs and mRNAs by online databases. We constructed a ceRNA network of 11 circRNAs, 14 miRNAs, and 33 mRNAs. The enrichment analysis showed that the positively circRNA-related mRNAs are mainly involved in the positive regulation of leukocyte activation and cell adhesion. It was revealed that circ_CDR1as and its target gene GATA6 were significantly downregulated in PSCC, and their reduction in tumor samples was validated by an external dataset and qRT-PCR, indicating a potential regulatory relationship between them. Our study identified that circ_CDR1as may affect PSCC progression through the circRNA-miRNA-mRNA network, and GATA6 could be one of its possible targets for PSCC therapy strategies.
阴茎鳞状细胞癌（PSCC）是一种恶性生殖肿瘤，环状RNA（circRNA）是癌症进展中的重要调节因子。然而，它们在PSCC中的具体作用尚未得到充分研究，其可通过竞争性内源RNA（ceRNA）网络发挥作用。我们收集了5份正常组织样本和6份PSCC组织样本进行全转录组RNA测序，获得了差异表达的环状RNA（DE-circRNA）和差异表达的信使RNA（DE-mRNA）。然后我们对它们进行了相关性分析，随后通过在线数据库对其靶微小RNA（miRNA）和mRNA进行预测和交集分析。我们构建了一个由11个circRNA、14个miRNA和33个mRNA组成的ceRNA网络。富集分析表明，与circRNA呈正相关的mRNA主要参与白细胞活化和细胞黏附的正调控。研究发现，circ_CDR1as及其靶基因GATA6在PSCC中显著下调，通过外部数据集和qRT-PCR验证了它们在肿瘤样本中的减少，表明它们之间存在潜在的调控关系。我们的研究表明，circ_CDR1as可能通过circRNA-miRNA-mRNA网络影响PSCC进展，GATA6可能是PSCC治疗策略的潜在靶点之一。
