Aqp1 overexpression may enhance glioma tumorigenesis by interacting with the transcriptional regulation networks of Foxo4, Maz, and E2F families

Gliomas is the most common and aggressive primary brain tumor. The C6 glioma cell line has been widely used for decades as experimental model system for the study of glioblastoma growth and invasion. Recently, aquaporin-1 (Aqp1) is reported to facilitate cell migration and potentially involved in tumor progression. Here we overexpressed Aqp1 in C6 cells to examine its potential role in glioblastoma. We found overexpression of Aqp1 in C6 cells significantly increased cell viability and cell migration. The upregulated genes were enriched for cell mobility and glioblastoma. Transcriptional factor binding analysis indicates the upregulated genes were regulated by FOXO4, MAZ, and E2F TF families, which are known factors involved in cell cycle control and cancer progression. Our study suggests Aqp1 is potentially involved in gliomas formation by interacting with the transcriptional regulation networks of FOXO4, MAZ, and E2F TF families.胶质瘤（Gliomas）是最常见且极具侵袭性的原发性脑肿瘤。数十年来，C6胶质瘤细胞系一直被广泛用作研究胶质母细胞瘤生长与侵袭的实验模型体系。近期有研究报道，水通道蛋白-1（aquaporin-1, Aqp1）可促进细胞迁移，且可能参与肿瘤进展过程。本研究通过在C6细胞中过表达Aqp1，探究其在胶质母细胞瘤中的潜在作用。研究发现，在C6细胞中过表达Aqp1可显著提升细胞活力与细胞迁移能力。上调基因的功能富集分析显示，其显著富集于细胞迁移调控及胶质母细胞瘤相关生物学过程。转录因子结合分析结果表明，上述上调基因受FOXO4、MAZ及E2F转录因子（Transcription Factor, TF）家族调控，而这些因子均为已知的细胞周期调控与肿瘤进展相关关键因子。本研究表明，Aqp1可能通过调控FOXO4、MAZ及E2F转录因子家族的转录调控网络，参与胶质瘤的发生发展。