Pediatric adrenocortical tumors (ACTs) are rare, highly heterogeneous neoplasms with limited therapeutic options, making the investigation of new targets with potential therapeutic or prognostic purposes urgent. ThePRKAB2gene produces one of the subunits of the AMP-activated protein kinase (AMPK) complex and has been associated with cancer. However, little is known about the role AMPK plays in ACTs. We have evaluated howPRKAB2is associated with clinical and biological characteristics in 63 pediatric patients with ACTs and conducted in vitro studies on the human NCI-H295R ACC cell line. An analysis of our cohort and the public ACC pediatric dataset GSE76019 showed that lowerPRKAB2expression was associated with relapse, death, metastasis, and lower event-free and overall survival rates. Multivariate analysis showed thatPRKAB2expression was an independent prognostic factor when associated with age, tumor weight and volume, and metastasis. In vitro tests on NCI-H295R cells demonstrated that Rottlerin, a drug that can activate AMPK, modulated several pathways in NCI-H295R cells, including AMPK/mTOR, Wnt/β-catenin, SKP2, HH, MAPK, NFKB, and TNF. Treatment with Rottlerin decreased cell proliferation and migration, clonogenic capacity, and steroid production. Together, these results suggest thatPRKAB2is a potential prognostic marker in pediatric ACTs, and that Rottlerin is promising for investigating drugs that can act against ACTs.
儿童肾上腺皮质肿瘤（ACTs）是一种罕见且高度异质性的肿瘤，治疗选择有限，因此迫切需要探索具有潜在治疗或预后价值的新靶点。PRKAB2基因编码AMP激活蛋白激酶（AMPK）复合物的一个亚基，该基因已被证实与癌症相关。然而，AMPK在ACTs中的作用尚不明确。本研究通过对63例儿童ACTs患者进行分析，评估了PRKAB2与临床及生物学特征之间的关联，并利用人源NCI-H295R ACC细胞系进行了体外实验。对研究队列及公共儿童ACC数据集GSE76019的分析显示，PRKAB2低表达与肿瘤复发、死亡、转移以及较低的无事件生存率和总生存率相关。多变量分析表明，PRKAB2表达是与年龄、肿瘤重量和体积以及转移状态相关的独立预后因素。在NCI-H295R细胞中进行的体外实验表明，能够激活AMPK的药物Rottlerin可调控多条信号通路，包括AMPK/mTOR、Wnt/β-catenin、SKP2、HH、MAPK、NFKB和TNF通路。Rottlerin处理可抑制细胞增殖与迁移、克隆形成能力及类固醇生成。综上，这些结果表明PRKAB2是儿童ACTs的潜在预后标志物，而Rottlerin为研发抗ACTs药物提供了有前景的研究方向。
肿瘤(癌症)患者之家