Wang Zhiyong, Qiao Xinwei, Xue Kaming, Chen Qianzhi, Li Anshu
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Commun Biol. 2025 Mar 25;8(1):489. doi: 10.1038/s42003-025-07930-2.
PTOV1 is recognized to have a significant role in various human cancers, including prostate cancer. However, it remains unclear what its clinical significance and biological role are in colorectal cancer (CRC). TCGA, NCBI/GEO, and Kaplan-Meier plot database mining provided important clues into the function and clinical importance of PTOV1 in CRC. Western blotting, immunohistochemistry, and immunofluorescence were utilized to discover PTOV1 protein levels in CRC cell lines and tissues. To explore the involvement of PTOV1 in the development of CRC and the underlying mechanisms, several in-vitro and in-vivo studies were executed, such as CCK-8 assays, colony formation, transwell assays, qRT-PCR, Co-IP, GST pull-down, immunostaining, and mouse xenograft assays. It was shown that PTOV1 expression level was upregulated in the tissues and cells of human CRC. PTOV1 high-expression level was associated with short survival. ZNF449 interacted with PTOV1 and accelerated CRC development in vitro and in vivo. Through Co-IP and GST pull-down studies, the physical interaction of PTOV1/ZNF449 was demonstrated. Furthermore, PTOV1 directly bound ZNF449, and this complex synergistically promoted the transcription of MYC. In addition, the PTOV1/ZNF449 interaction was disrupted by the TAT- PTOV1 (125-283 aa) protein leading to inhibit the CRC development in a xenografted mouse model. According to these findings, PTOV1 has an essential role in CRC progression, and PTOV1/ZNF449 interaction could be a possible therapeutic target for CRC.
PTOV1被认为在包括前列腺癌在内的多种人类癌症中发挥重要作用。然而，其在结直肠癌（CRC）中的临床意义和生物学作用仍不清楚。通过对TCGA、NCBI/GEO以及Kaplan-Meier plot数据库的挖掘，为PTOV1在CRC中的功能和临床重要性提供了重要线索。利用蛋白质免疫印迹法、免疫组织化学和免疫荧光法检测CRC细胞系和组织中PTOV1蛋白水平。为了探究PTOV1在CRC发生发展中的作用及潜在机制，开展了多项体外和体内研究，如CCK-8检测、集落形成实验、Transwell实验、qRT-PCR、免疫共沉淀、GST下拉实验、免疫染色以及小鼠异种移植实验。结果表明，PTOV1在人类CRC组织和细胞中的表达水平上调。PTOV1高表达与生存期短相关。ZNF449与PTOV1相互作用，在体外和体内加速CRC的发展。通过免疫共沉淀和GST下拉实验，证实了PTOV1/ZNF449的物理相互作用。此外，PTOV1直接结合ZNF449，该复合物协同促进MYC的转录。此外，TAT-PTOV1（125-283 aa）蛋白破坏了PTOV1/ZNF449的相互作用，导致异种移植小鼠模型中CRC的发展受到抑制。根据这些发现，PTOV1在CRC进展中起重要作用，PTOV1/ZNF449相互作用可能是CRC的一个潜在治疗靶点。
