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新的胰腺癌生物标志物 eIF1、eIF2D、eIF3C 和 eIF6 在导管腺癌的翻译调控中发挥主要作用。

New Pancreatic Cancer Biomarkers eIF1, eIF2D, eIF3C and eIF6 Play a Major Role in Translational Control in Ductal Adenocarcinoma.

机构信息

Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.

Institute of Dermatology and Venerology, Medical University of Graz, Graz, Austria.

出版信息

Anticancer Res. 2020 Jun;40(6):3109-3118. doi: 10.21873/anticanres.14292.

Abstract

BACKGROUND/AIM: Pancreatic cancer is one of the deadliest forms of cancer and ranks among the leading causes of cancer-related death worldwide. The most common histological type is ductal adenocarcinoma (PDAC), accounting for approximately 95% of cases. Deregulation of protein synthesis has been found to be closely related to cancer. The rate-limiting step of translation is initiation, which is regulated by a broad range of eukaryotic translation initiation factors (eIFs).

PATIENTS AND METHODS

Human PDAC samples were biochemically analyzed for the expression of various eIF subunits on the protein level (immunohistochemistry, immunoblot analyses) in 174 cases of PDAC in comparison with non-neoplastic pancreatic tissue (n=10).

RESULTS

Our investigation revealed a significant down-regulation of four specific eIF subunits, namely eIF1, eIF2D, eIF3C and eIF6. Concomitantly, the protein (immunoblot) levels of eIF1, eIF2D, eIF3C and eIF6 were reduced in PDAC samples as compared with non-neoplastic pancreatic tissue.

CONCLUSION

Members of the eIF family are of relevance in pancreatic tumor biology and may play a major role in translational control in PDAC. Consequently, they might be useful as potential new biomarkers and therapeutic targets in PDAC.

摘要

背景/目的:胰腺癌是最致命的癌症之一,也是全球癌症相关死亡的主要原因之一。最常见的组织学类型是导管腺癌(PDAC),约占 95%的病例。已经发现蛋白质合成的失调与癌症密切相关。翻译的限速步骤是起始,它受到广泛的真核翻译起始因子(eIFs)的调节。

患者和方法

在 174 例 PDAC 病例中,与非肿瘤性胰腺组织(n=10)相比,通过生物化学方法分析了各种 eIF 亚基在蛋白质水平(免疫组织化学、免疫印迹分析)上的表达。

结果

我们的研究表明,四个特定的 eIF 亚基,即 eIF1、eIF2D、eIF3C 和 eIF6 的表达显著下调。同时,与非肿瘤性胰腺组织相比,PDAC 样本中的 eIF1、eIF2D、eIF3C 和 eIF6 的蛋白(免疫印迹)水平降低。

结论

eIF 家族成员与胰腺肿瘤生物学有关,可能在 PDAC 中的翻译控制中发挥重要作用。因此,它们可能是 PDAC 中潜在的新生物标志物和治疗靶点。

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