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eEF1A1 促进结直肠癌的进展并预测患者的不良预后。

eEF1A1 promotes colorectal cancer progression and predicts poor prognosis of patients.

机构信息

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.

出版信息

Cancer Med. 2023 Jan;12(1):513-524. doi: 10.1002/cam4.4848. Epub 2022 May 24.

Abstract

Colorectal cancer (CRC) is a major leading cause of cancer mortality worldwide in which dysregulated protein synthesis plays an etiologic role. The eukaryotic elongation factor 1 A1 (eEF1A1) exerts significant effects on protein synthesis by contributing to peptide chain extension. Whereas its role in CRC remains to be investigated. In this study, we found that the mRNA and protein levels of eEF1A1 were significantly upregulated in CRC cell lines and tissues. Elevated expression of eEF1A1 was correlated with shorter overall survival in 94 CRC patients. The inhibition of proliferation and cell cycle block were observed in CRC cells after eEF1A1 downregulation. Mechanistically, weighted gene correlation network analysis and further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that mitogen-activated protein kinases (MAPKs) signaling pathways were significantly enriched in high-eEF1A1 expression group, and the levels of phosphorylated p38/JNK/ERK MAPK were dramatically decreased after eEF1A1 downregulation. Overexpression of eEF1A1 in CRC correlated with a poor prognosis. Collectively, this study determined the oncogenic role of eEF1A1 in CRC proliferation and tumorigenesis. eEF1A1 might be a promising therapeutic target and prognostic biomarker in CRC.

摘要

结直肠癌(CRC)是全球癌症死亡的主要原因,其中蛋白质合成失调起着病因学作用。真核延伸因子 1A1(eEF1A1)通过促进肽链延伸对蛋白质合成产生重大影响。然而,其在 CRC 中的作用仍有待研究。在这项研究中,我们发现 eEF1A1 的 mRNA 和蛋白水平在 CRC 细胞系和组织中显著上调。94 名 CRC 患者的整体生存时间与 eEF1A1 的表达水平呈负相关。eEF1A1 下调后观察到 CRC 细胞增殖受到抑制和细胞周期阻滞。机制上,加权基因相关网络分析和进一步的京都基因与基因组百科全书(KEGG)分析表明,有丝分裂原激活的蛋白激酶(MAPKs)信号通路在高 eEF1A1 表达组中明显富集,eEF1A1 下调后磷酸化 p38/JNK/ERK MAPK 的水平显著降低。CRC 中 eEF1A1 的过表达与预后不良相关。总之,这项研究确定了 eEF1A1 在 CRC 增殖和肿瘤发生中的致癌作用。eEF1A1 可能是 CRC 有前途的治疗靶点和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b10/9844609/9a94bef5e342/CAM4-12-513-g004.jpg

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