HMGB1 和 HMGB2 对神经内分泌和腺癌前列腺癌模型转录调控的影响不同。
The Effect of HMGB1 and HMGB2 on Transcriptional Regulation Differs in Neuroendocrine and Adenocarcinoma Models of Prostate Cancer.
机构信息
Centro Interdisciplinar de Química e Bioloxía (CICA), Campus de Elviña, Universidade da Coruña, As Carballeiras, s/n, 15071 A Coruña, Spain.
Facultade de Ciencias, Campus de A Zapateira, Universidade da Coruña, A Fraga, s/n, 15071 A Coruña, Spain.
出版信息
Int J Mol Sci. 2024 Mar 7;25(6):3106. doi: 10.3390/ijms25063106.
Human high-mobility group-B (HMGB) proteins regulate gene expression in prostate cancer (PCa), a leading cause of oncological death in men. Their role in aggressive PCa cancers, which do not respond to hormonal treatment, was analyzed. The effects of and silencing upon the expression of genes previously related to PCa were studied in the PCa cell line PC-3 (selected as a small cell neuroendocrine carcinoma, SCNC, PCa model not responding to hormonal treatment). A total of 72% of genes analyzed, using pre-designed primer panels, were affected. HMGB1 behaved mostly as a repressor, but HMGB2 as an activator. Changes in , , , and expression were validated using qRT-PCR after silencing or overexpression in PC-3 and LNCaP (selected as an adenocarcinoma model of PCa responding to hormonal treatment) cell lines. Similarly, the regulatory role of upon , , , , and expression was validated, finding differences between cell lines. The correlation between the expression of , , and their targets was analyzed in PCa patient samples and also in PCa subgroups, classified as neuroendocrine positive or negative, in public databases. These results allow a better understanding of the role of HMGB proteins in PCa and contribute to find specific biomarkers for aggressive PCa.
人高迁移率族蛋白 B（HMGB）蛋白调节前列腺癌（PCa）中的基因表达，这是男性肿瘤死亡的主要原因。分析了它们在不响应激素治疗的侵袭性 PCa 癌症中的作用。在 PC-3（选择作为不响应激素治疗的小细胞神经内分泌癌，SCNC 的 PCa 模型）细胞系中研究了 和 沉默对先前与 PCa 相关的基因表达的影响。使用预设计的引物组分析了总共 72%的基因，HMGB1 主要表现为抑制剂，但 HMGB2 为激活剂。在 PC-3 和 LNCaP（选择作为对激素治疗有反应的 PCa 的腺癌模型）细胞系中沉默或过表达后，使用 qRT-PCR 验证了 、 、 、 和 的表达变化。同样，验证了 对 、 、 、 和 的表达的调节作用，发现细胞系之间存在差异。分析了 PCa 患者样本中 、 及其靶基因的表达之间的相关性，还在公共数据库中分析了根据神经内分泌阳性或阴性分类的 PCa 亚组。这些结果有助于更好地理解 HMGB 蛋白在 PCa 中的作用，并有助于找到侵袭性 PCa 的特异性生物标志物。
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