Identification of therapeutic targets and prognostic biomarkers from the hnRNP family in invasive breast carcinoma.
Identification of therapeutic targets and prognostic biomarkers from the hnRNP family in invasive breast carcinoma.
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侵袭性乳腺癌中 hnRNP 家族治疗靶点和预后生物标志物的鉴定
DOI：
10.18632/aging.202411
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发表时间：
2021-01-20
期刊：
影响因子：
--
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Zhou J;Guo Y;Huo Z;Xing Y;Fang J;Ma G;Han Q;Wang M;Xu Q
异质性核糖核蛋白(HnRNPs)是一种RNA结合蛋白，在多种恶性肿瘤的发病过程中发挥着重要作用。然而，它们在浸润性乳腺癌(BRCA)中的表达模式、临床应用意义和预后价值尚不清楚。在本研究中，我们利用Oncomine4.5、UALCAN门户网站和其他可用的数据库中积累的数据，对BRCA中的hnRNP家族成员进行了调查。我们探讨hnRNPs在BRCA中的表达及其预后价值。我们进一步分析了它们与BRCA患者临床病理特征的关系。随后，我们计算了hnRNPs的改变频率，构建了hnRNPs的相互作用网络，并检测了hnRNPs的潜在共表达基因，揭示了HNRNPU和SYNCRIP是BRCA的核心分子基因，需要进一步研究。我们验证了免疫组织化学(IHC)模式，以模拟基于病理学的临床应用。体外细胞功能实验表明，HNRNPU能促进上皮细胞向间充质细胞转化，对侵袭性BRCA细胞具有功能性刺激侵袭能力和抑制活性的作用。综上所述，我们的系统分析表明，HNRNPU是在BRCA转移中起基础作用的关键分子，这可能有助于开发新的诊断和预后标志物来分析BRCA的进展。
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins that are reported to play a crucial role in the pathogenic process of multiple malignancies. However, their expression patterns, clinical application significance and prognostic values in invasive breast carcinoma (BRCA) remain unknown. In this study, we investigated hnRNP family members in BRCA using accumulated data from Oncomine 4.5, UALCAN Web portal and other available databases. We explored the expression and prognostic value level of hnRNPs in BRCA. We further analyzed their association with the clinicopathological features of BRCA patients. Subsequently, we calculated the alteration frequency of hnRNPs, constructed the interaction network of hnRNPs, and examined the potential coexpression genes of hnRNPs, revealing that HNRNPU and SYNCRIP are the core molecular genes requiring further investigation for BRCA. We validated the immunohistochemistry (IHC) pattern to simulate clinical applications based on pathology. Cell function experiments conducted in vitro indicated that HNRNPU can promote epithelial-mesenchymal transition, functionally stimulating the invasion capacity and inhibiting the viability of invasive BRCA cells. In summary, our systematic analysis demonstrated that HNRNPU was the key molecule that played a fundamental role in BRCA metastasis, which may facilitate the development of new diagnostic and prognostic markers for the analysis of BRCA progression.
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