DNAJB6 促进食管鳞癌中的铁死亡。
DNAJB6 Promotes Ferroptosis in Esophageal Squamous Cell Carcinoma.
机构信息
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Department of Thoracic Surgery, Jinan City People's Hospital, Laiwu, Shandong, China.
出版信息
Dig Dis Sci. 2020 Jul;65(7):1999-2008. doi: 10.1007/s10620-019-05929-4. Epub 2019 Nov 8.
BACKGROUND
DnaJ/Hsp40 homolog, subfamily B, member 6 (DNAJB6) is significantly down-regulated in esophageal squamous cell carcinoma (ESCC), while its complicated molecular mechanisms are still unknown.
AIMS
To investigate the relationship between DNAJB6 and ESCC.
METHODS
The expression of DNAJB6 was detected in ESCC patient by Western blot and immunohistochemistry. To overexpress DNAJB6a by lentivirus infection, colony-forming, CCK-8, transwell, mouse xenograft assays were utilized to verify the proliferous, invasive, and migratory role of DNAJB6a in ESCC cells. The MDA and GSH assays determine whether DNAJB6a participates in cell redox reaction. The variation of AKT and GPX4 was detected by Western blot.
RESULTS
The correlation between DNAJB6 level and lymph node metastasis in ESCC patient was negative. Overexpressing DNAJB6a shows tumor-suppressive effects in vitro and in vivo. In addition, DNAJB6a overexpression was accompanied together with a remarkable reduction in the protein levels of GPX4 and phosphorylated AKT (p-AKT).
CONCLUSION
DNAJB6 plays an important anti-oncogenic role in ESCC evolvement via ferroptosis.
背景
DNAJ/Hsp40 同源物家族 B 成员 6（DNAJB6）在食管鳞状细胞癌（ESCC）中显著下调，但其复杂的分子机制尚不清楚。
目的
研究 DNAJB6 与 ESCC 的关系。
方法
通过 Western blot 和免疫组织化学检测 ESCC 患者中 DNAJB6 的表达。通过慢病毒感染过表达 DNAJB6a，利用集落形成、CCK-8、Transwell 实验和小鼠异种移植实验验证 DNAJB6a 在 ESCC 细胞中的增殖、侵袭和迁移作用。MDA 和 GSH 测定法确定 DNAJB6a 是否参与细胞氧化还原反应。Western blot 检测 AKT 和 GPX4 的变化。
结果
DNAJB6 水平与 ESCC 患者的淋巴结转移呈负相关。过表达 DNAJB6a 在体外和体内均显示出肿瘤抑制作用。此外，DNAJB6a 的过表达伴随着 GPX4 和磷酸化 AKT（p-AKT）蛋白水平的显著降低。
结论
DNAJB6 通过铁死亡在 ESCC 发生发展中发挥重要的抑癌作用。
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