RNA结合蛋白47的下调可预测患者的低生存率,并通过RNA稳定性修饰促进肾细胞恶性肿瘤的发展。

IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular biomedicine Pub Date : 2023-11-14 DOI:10.1186/s43556-023-00148-w
Cheng Wang, Weiquan Li, Xiangui Meng, Hongwei Yuan, Tiexi Yu, Wei Yang, Dong Ni, Lei Liu, Wen Xiao
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引用次数: 0

摘要

RNA结合蛋白(rbp)在疾病或正常生理过程中对细胞功能、组织生长和疾病发展至关重要。RNA结合基序蛋白47 (RBM47)已被证实对多种肿瘤具有抗肿瘤作用,但其在肾癌中的作用尚不清楚。在这里,我们通过生物信息学分析证明了RBM47在透明细胞肾癌(ccRCC)的公共数据库和临床样本中的表达和预后作用。通过基因功能预测和体外实验验证了RBM47在肾癌中的可能机制。结果显示,与对照组相比,RBM47在肾癌中表达下调。RBM47低表达提示ccRCC预后较差。与正常肾小管上皮细胞相比,RBM47在肾癌细胞系中的表达明显降低。基因集富集分析表明,上皮间质转化(epithelial - mesenchal transition, EMT)和转化生长因子-β信号通路与ccRCC中RBM47相关。RBM47的表达与e-cadherin呈正相关,与snail和vimentin呈负相关。RBM47过表达可抑制肾癌细胞的迁移、侵袭活性和增殖能力,抑制RBM47可通过RNA稳定性修饰的EMT信号传导促进恶性特征的发展。因此,我们的研究结果表明,RBM47作为一种新的分子生物标志物,可能在ccRCC的癌变过程中发挥关键作用。
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Downregulation of RNA binding protein 47 predicts low survival in patients and promotes the development of renal cell malignancies through RNA stability modification.

RNA binding proteins (RBPs) are crucial for cell function, tissue growth, and disease development in disease or normal physiological processes. RNA binding motif protein 47 (RBM47) has been proven to have anti-tumor effects on many cancers, but its effect is not yet clear in renal cancer. Here, we demonstrated the expression and the prognostic role of RBM47 in public databases and clinical samples of clear cell renal carcinoma (ccRCC) with bioinformatics analysis. The possible mechanism of RBM47 in renal cancer was verified by gene function prediction and in vitro experiments. The results showed that RBM47 was downregulated in renal cancers when compared with control groups. Low RBM47 expression indicated poor prognosis in ccRCC. RBM47 expression in renal cancer cell lines was reduced significantly when compared to normal renal tubular epithelial cells. Epithelial-mesenchymal transition (EMT) and transforming growth factor-β signaling pathway was associated with RBM47 in ccRCC by Gene set enrichment analysis. RBM47 expression had a positive correlation with e-cadherin, but a negative correlation with snail and vimentin. RBM47 overexpression could repress the migration, invasion activity, and proliferation capacity of renal cancer cells, while RBM47 inhibition could promote the development of the malignant features through EMT signaling by RNA stability modification. Therefore, our results suggest that RBM47, as a new molecular biomarker, may play a key role in the cancer development of ccRCC.

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