Frontiers in Endocrinology ( IF 3.9 ) Pub Date : 2022-01-21 , DOI: 10.3389/fendo.2021.706909 Kejing Zhu 1, 2, 3, 4 , Xueting Cheng 5 , Shuman Wang 4 , Hong Zhang 1 , Yu Zhang 4 , Xiong Wang 1 , Yonggang Chen 1 , Jinhu Wu 1
Prolactinoma is the most common type of pituitary tumors, and its resultant tumor occupying and hormone disturbance greatly damage the health of patients. In this study, we investigated a protein kinase-PDZ Binding Kinase (PBK)/T-LAK Cell-Originated Protein Kinase (TOPK) as a candidate protein regulating prolactin (PRL) secretion and tumor growth of prolactinomas.
Downloaded prolactinoma transcriptome dataset from Gene Expression Omnibus (GEO) database, and screened differentially expressed genes (DEGs) between normal pituitary tissues and prolactinoma tissues. Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed, a protein-protein interaction (PPI) network was constructed and the hub genes were identified. After a literature search, TOPK was presumed as an candidate target regulating the prolactinoma. We found a specific inhibitor of TOPK to investigate its effects on the proliferation, migration, apoptosis and PRL secretion of pituitary tumor cells. Finally, the regulation of TOPK inhibitor on its downstream target-p38 Mitogen Activated Protein Kinase (p38 MAPK) was detected to explore the potential mechanism.
A total of 361 DEGs were identified, and 20 hub genes were screened out. TOPK inhibitor HI-TOPK-032 could suppress the proliferation & migration and induce apoptosis of pituitary tumor cells
Our study of identification and functional validation of TOPK suggests that this candidate can be a promising molecular target for prolactinoma treatment.
中文翻译:
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PBK/TOPK 抑制剂抑制泌乳素瘤的进展
泌乳素瘤是最常见的垂体肿瘤类型,其引起的肿瘤占位和激素紊乱极大地损害了患者的健康。在这项研究中,我们研究了蛋白激酶-PDZ 结合激酶 (PBK)/T-LAK 细胞源蛋白激酶 (TOPK) 作为调节催乳素 (PRL) 分泌和催乳素瘤肿瘤生长的候选蛋白。
从基因表达综合(GEO)数据库下载催乳素瘤转录组数据集,筛选正常垂体组织和催乳素瘤组织之间的差异表达基因(DEGs)。然后,对DEG进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析,构建蛋白质-蛋白质相互作用(PPI)网络并鉴定中心基因。经过文献检索,TOPK 被推测为调节催乳素瘤的候选靶点。我们发现了一种特异性的 TOPK 抑制剂,以研究其对垂体肿瘤细胞增殖、迁移、凋亡和 PRL 分泌的影响。最后,检测了TOPK抑制剂对其下游靶标-p38丝裂原活化蛋白激酶(p38 MAPK)的调节作用,以探索其潜在机制。
共鉴定出361个DEG,筛选出20个hub基因。TOPK 抑制剂 HI-TOPK-032 可抑制垂体肿瘤细胞的增殖和迁移并诱导其凋亡
我们对 TOPK 的鉴定和功能验证的研究表明,该候选物可能是催乳素瘤治疗的有希望的分子靶点。