Wang Chuyue, Zhao Yingying, Chen You, Shi Ying, Yang Zhiying, Wu Weili, Ma Rui, Wang Bo, Sun Yifeng, Yuan Ping
Guangdong Institute of Gastroenterology, Guangzhou, China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Cancer Res Treat. 2025 Jan;57(1):212-228. doi: 10.4143/crt.2024.408. Epub 2024 Aug 9.
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
癌症已成为重大的公共卫生问题，因此发现新的癌症标志物或治疗靶点极为重要。在某些类型的癌症中已观察到肿瘤坏死因子受体超家族成员12A（TNFRSF12A）表达升高。本项目旨在研究TNFRSF12A在肿瘤中的功能及其潜在机制。
利用各种网站进行生物信息学分析。建立了稳定敲低或过表达TNFRSF12A的肿瘤细胞系，用于细胞表型实验和在BALB/c小鼠中进行皮下肿瘤形成实验。采用RNA测序来研究TNFRSF12A的机制。
TNFRSF12A在大多数癌症中上调，并与预后不良相关。敲低TNFRSF12A可阻碍结直肠癌进展，而过表达则在体外和体内均促进恶性肿瘤发生。TNFRSF12A过表达导致核因子κB（NF-κB）信号增加以及含杆状病毒IAP重复序列3（BIRC3）显著上调，BIRC3是NF-κB成员RELA的转录靶点，并且经实验证实是TNFRSF12A的关键下游因子。因此，我们推测在结直肠癌中存在TNFRSF12A/RELA/BIRC3调控轴。
TNFRSF12A在多种癌症类型中上调，并与预后不良相关。在结直肠癌中，TNFRSF12A表达升高可能通过TNFRSF12A/RELA/BIRC3调控轴促进肿瘤生长。
