Identification of an mRNA isoform switch for HNRNPA1 in breast cancers

Roles of HNRNPA1 are beginning to emerge in cancers; however, mechanisms causing deregulation of HNRNPA1 function remain elusive. Here, we describe an isoform switch between the 3′-UTR isoforms of HNRNPA1 in breast cancers. We show that the dominantly expressed isoform in mammary tissue has a short...

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Published in:Scientific reports 2021-12, Vol.11 (1), p.24444-24444, Article 24444
Main Authors: Erdem, Murat, Ozgul, İbrahim, Dioken, Didem Naz, Gurcuoglu, Irmak, Guntekin Ergun, Sezen, Cetin-Atalay, Rengul, Can, Tolga, Erson-Bensan, Ayse Elif
Format: Article
Language:English
Subjects:
3' Untranslated Regions
631/337
631/337/572
631/67/1347
Breast cancer
Breast Neoplasms - genetics
Cancer
Cell Line, Tumor
Deregulation
Female
Gene expression
Gene Expression Regulation, Neoplastic
Heterogeneous Nuclear Ribonucleoprotein A1 - genetics
Humanities and Social Sciences
Humans
Isoforms
MicroRNAs - genetics
miRNA
multidisciplinary
Phenotypes
RNA Isoforms - genetics
RNA, Messenger - genetics
Science
Science (multidisciplinary)
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Summary:Roles of HNRNPA1 are beginning to emerge in cancers; however, mechanisms causing deregulation of HNRNPA1 function remain elusive. Here, we describe an isoform switch between the 3′-UTR isoforms of HNRNPA1 in breast cancers. We show that the dominantly expressed isoform in mammary tissue has a short half-life. In breast cancers, this isoform is downregulated in favor of a stable isoform. The stable isoform is expressed more in breast cancers, and more HNRNPA1 protein is synthesized from this isoform. High HNRNPA1 protein levels correlate with poor survival in patients. In support of this, silencing of HNRNPA1 causes a reversal in neoplastic phenotypes, including proliferation, clonogenic potential, migration, and invasion. In addition, silencing of HNRNPA1 results in the downregulation of microRNAs that map to intragenic regions. Among these miRNAs, miR-21 is known for its transcriptional upregulation in breast and numerous other cancers. Altogether, the cancer-specific isoform switch we describe here for HNRNPA1 emphasizes the need to study gene expression at the isoform level in cancers to identify novel cases of oncogene activation.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-04007-y