Tian Zeyu, Liu Qi, Luo Jihui, Ning Ning, Qu Jing
Department of General Surgery, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, 410006, Hunan, China.
Medical Equipment Department, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, 410005, Hunan, China.
Discov Oncol. 2025 Jun 12;16(1):1076. doi: 10.1007/s12672-025-02803-w.
This study investigates the role of HSPB1 in pancreatic cancer, particularly its impact on cell proliferation and migration through ferroptosis regulation and interaction with TP53 MATERIALS AND METHODS: HSPB1 expression was analyzed using BioGPS and GEPIA databases. BxPC-3 cell lines with stable HSPB1 overexpression and knockdown were created via plasmid transfection and siRNA. The study examined HSPB1's effect on TP53 protein levels and its role in ferroptosis using TP53 agonists and inhibitors.
HSPB1 mRNA levels were significantly elevated in pancreatic cancer tissues, and both mRNA and protein levels were notably upregulated in cancer cell lines. HSPB1 overexpression promoted BxPC-3 cell proliferation and migration, while silencing HSPB1 reduced these effects. High HSPB11 expression increased the levels of SLC7A11 and GPX4, while HSPB1 knockdown inhibited their expression. Transmission electron microscopy (TEM) showed that HSPB1 overexpression alleviated erastin-induced cellular damage. Although HSPB1 did not significantly affect TP53 mRNA levels, it reduced the degradation of TP53 protein, thereby enhancing the expression of SLC7A11 and GPX4 and reducing ferroptosis. The TP53 agonist significantly attenuated the effects of HSPB1 overexpression on SLC7A11 and GPX4 expression and partially restored TP53 expression. The TP53 inhibitor reversed the decrease in SLC7A11 and GPX4 expression caused by HSPB1 silencing and reduced the elevated levels of ROS and free iron. Moreover, HSPB1 overexpression reduced lipid ROS production.
HSPB1 promotes pancreatic cancer progression by suppressing TP53 signaling and increasing SLC7A11 and GPX4 expression, attenuating ferroptosis. These insights suggest HSPB1 as a potential therapeutic target, warranting further development of specific inhibitors.
本研究探讨热休克蛋白B1（HSPB1）在胰腺癌中的作用，特别是其通过铁死亡调节及与TP53相互作用对细胞增殖和迁移的影响。材料与方法：利用BioGPS和GEPIA数据库分析HSPB1的表达情况。通过质粒转染和小干扰RNA（siRNA）构建HSPB1过表达和敲低的稳定BxPC-3细胞系。本研究使用TP53激动剂和抑制剂检测HSPB1对TP53蛋白水平的影响及其在铁死亡中的作用。
胰腺癌组织中HSPB1 mRNA水平显著升高，癌细胞系中mRNA和蛋白水平均明显上调。HSPB1过表达促进BxPC-3细胞增殖和迁移，而沉默HSPB1则降低这些作用。高HSPB1表达增加了溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4）的水平，而敲低HSPB1则抑制其表达。透射电子显微镜（TEM）显示，HSPB1过表达减轻了埃拉斯汀诱导的细胞损伤。虽然HSPB1对TP53 mRNA水平无显著影响，但它减少了TP53蛋白的降解，从而增强了SLC7A11和GPX4的表达并减少了铁死亡。TP53激动剂显著减弱了HSPB1过表达对SLC7A11和GPX4表达的影响，并部分恢复了TP53表达。TP53抑制剂逆转了HSPB1沉默导致的SLC7A11和GPX4表达降低，并降低了活性氧（ROS）和游离铁的升高水平。此外，HSPB1过表达减少了脂质ROS的产生。
HSPB1通过抑制TP53信号传导并增加SLC7A11和GPX4表达、减轻铁死亡来促进胰腺癌进展。这些见解表明HSPB1是一个潜在的治疗靶点，值得进一步研发特异性抑制剂。
