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NORAD- pumilio调控轴作为乳腺癌生物标志物的潜力

The Potential of NORAD-PUMILIO- Regulatory Axis as a Biomarker in Breast Cancer.

作者信息

Muller Cristiane Sato Mara, Giner Igor Samesima, Zambalde Érika Pereira, Carvalho Tamyres Mingorance, Ribeiro Enilze Maria de Souza Fonseca, Carvalho de Oliveira Jaqueline, Mathias Carolina, Gradia Daniela Fiori

机构信息

Laboratory of Human Cytogenetics and Oncogenetics, Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.

Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, Brazil.

出版信息

Noncoding RNA. 2022 Nov 10;8(6):76. doi: 10.3390/ncrna8060076.

Abstract

: Long non-coding RNAs (LncRNA) represent a heterogeneous family of RNAs that have emerged as regulators of various biological processes through their association with proteins in ribonucleoproteins complexes. The dynamic of these interactions can affect cell metabolism, including cancer development. Annually, breast cancer causes thousands of deaths worldwide, and searching for new biomarkers is pivotal for better diagnosis and treatment. : Based on in silico prediction analysis, we focus on LncRNAs that have binding sites for PUMILIO, an RBP family involved in post-transcriptional regulation and associated with cancer progression. We compared the expression levels of these LncRNAs in breast cancer and non-tumor samples from the TCGA database. We analyzed the impact of overall and disease-free survival associated with the expression of the LncRNAs and co-expressed genes and targets of PUMILIO proteins. : Our results found NORAD as the most relevant LncRNA with a PUMILIO binding site in breast cancer, differently expressed between Luminal A and Basal subtypes. Additionally, NORAD was co-expressed in a Basal-like subtype (0.55) with the gene, a target gene of PUMILIO related to chromosome stability during cell division. : These data suggest that this molecular axis may provide insights for developing novel therapeutic strategies for breast cancer.

摘要

长链非编码RNA(LncRNA)代表了一类异质性的RNA家族,它们通过与核糖核蛋白复合物中的蛋白质结合,成为各种生物过程的调节因子。这些相互作用的动态变化会影响细胞代谢,包括癌症的发展。每年,乳腺癌在全球导致数千人死亡,寻找新的生物标志物对于更好的诊断和治疗至关重要。基于计算机预测分析,我们聚焦于具有PUMILIO结合位点的LncRNA,PUMILIO是一个参与转录后调控并与癌症进展相关的RBP家族。我们比较了来自TCGA数据库的乳腺癌和非肿瘤样本中这些LncRNA的表达水平。我们分析了与LncRNA表达以及PUMILIO蛋白的共表达基因和靶标相关的总生存期和无病生存期的影响。我们的结果发现,NORAD是乳腺癌中最相关的具有PUMILIO结合位点的LncRNA,在Luminal A和基底亚型之间表达不同。此外,NORAD在基底样亚型(0.55)中与 基因共表达,该基因是PUMILIO的一个靶基因,与细胞分裂过程中的染色体稳定性有关。这些数据表明,这个分子轴可能为开发乳腺癌的新型治疗策略提供思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7d/9680495/78ea233307bb/ncrna-08-00076-g001.jpg

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