<br>hnRNP A1 和 hnRNP C 与甲状腺癌细胞中的 miR-17 和 miR-18 相关,FEBS Open Bio

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hnRNP A1 和 hnRNP C 与甲状腺癌细胞中的 miR-17 和 miR-18 相关
FEBS Open Bio ( IF 2.8 ) Pub Date : 2022-04-13 , DOI: 10.1002/2211-5463.13409
Maria Gabriela Pereira Dos Santos ₁ , Guilherme Henrique Gatti da Silva ₁ , Helder Yudi Nagasse ₁ , Cesar Seigi Fuziwara ₁ , Edna T Kimura ₁ , Patricia Pereira Coltri ₁

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异质核核糖核蛋白（hnRNP）是基因表达调节的重要参与者。二十种不同的 hnRNP 蛋白中的大多数通过调节前 mRNA 剪接发挥作用。大多数已被证明可以调节致瘤过程进展的关键基因的表达，并且还观察到在几种类型的癌症中过度表达。此外，这些蛋白质被描述为一些 microRNA (miRNA) 成熟的必需成分。在人类基因组中，超过70%的miRNA是从内含子转录而来的；因此，我们假设参与剪接的调节蛋白对于它们的成熟可能很重要。 miR-17-92簇表达的增加已被证明与许多癌症的发生有关，例如甲状腺癌、肺癌和淋巴瘤。在本文中，我们发现 BCPAP 甲状腺癌细胞中 hnRNP A1 和 hnRNP C 的过度表达直接影响miR-17-92 miRNA 的表达。两种蛋白均与该簇的 5' 端结合，强烈沉淀 miRNA miR-17和miR-18a并上调miR-92a的表达。在这些 hnRNP 过度表达后，BCPAP 细胞还表现出增殖、迁移和侵袭率增加，表明这些蛋白质和 miRNA 的上调与增强的致瘤表型有关。

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hnRNP A1 and hnRNP C associate with miR-17 and miR-18 in thyroid cancer cells

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are essential players in the regulation of gene expression. The majority of the twenty different hnRNP proteins act through the modulation of pre-mRNA splicing. Most have been shown to regulate the expression of critical genes for the progression of tumorigenic processes and were also observed to be overexpressed in several types of cancer. Moreover, these proteins were described as essential components for the maturation of some microRNAs (miRNAs). In the human genome, over 70% of miRNAs are transcribed from introns; therefore, we hypothesized that regulatory proteins involved with splicing could be important for their maturation. Increased expression of the miR-17-92 cluster has already been shown to be related to the development of many cancers, such as thyroid, lung, and lymphoma. In this article, we show that overexpression of hnRNP A1 and hnRNP C in BCPAP thyroid cancer cells directly affects the expression of miR-17-92 miRNAs. Both proteins associate with the 5′-end of this cluster, strongly precipitate miRNAs miR-17 and miR-18a and upregulate the expression of miR-92a. Upon overexpression of these hnRNPs, BCPAP cells also show increased proliferation, migration, and invasion rates, suggesting upregulation of these proteins and miRNAs is related to an enhanced tumorigenic phenotype.

更新日期：2022-04-13

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