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

Abstract

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.

RNA-binding proteins and exoribonucleases modulating miRNA in cancer: the enemy within

“…The normally processed mature miRNA miR-18a-3p acts as a tumor suppressor by targeting the K-Ras oncogene in ovarian cancer 30 . Similarly, hnRNP A1 can also directly bind to the 5′-ends of miR-17 and miR-18 in conjunction with hnRNP C in thyroid cancer cells, thereby upregulating the expression of those miRNAs and promoting tumorigenic properties 31 .

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