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鉴定乳腺癌中 HNRNPA1 的 mRNA 异构体转换。

Identification of an mRNA isoform switch for HNRNPA1 in breast cancers.

机构信息

Department of Biological Sciences, Middle East Technical University (METU), Dumlupinar Blv No: 1 Universiteler Mah., Cankaya, Ankara, 06800, Turkey.

Cancer Systems Biology Laboratory, CanSyL, Graduate School of Informatics, Middle East Technical University, 06800, Ankara, Turkey.

出版信息

Sci Rep. 2021 Dec 27;11(1):24444. doi: 10.1038/s41598-021-04007-y.

DOI:10.1038/s41598-021-04007-y
PMID:34961772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8712528/
Abstract

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.

摘要

HNRNPA1 的作用开始在癌症中显现；然而，导致 HNRNPA1 功能失调的机制仍然难以捉摸。在这里，我们描述了乳腺癌中 HNRNPA1 的 3'UTR 异构体之间的异构体转换。我们表明，在乳腺组织中表达的优势异构体半衰期短。在乳腺癌中，这种异构体下调有利于稳定的异构体。稳定的异构体在乳腺癌中表达更多，并且从这个异构体合成更多的 HNRNPA1 蛋白。高水平的 HNRNPA1 蛋白与患者的不良预后相关。支持这一点的是，沉默 HNRNPA1 导致肿瘤表型的逆转，包括增殖、集落形成潜力、迁移和侵袭。此外，沉默 HNRNPA1 导致映射到基因内区域的 microRNAs 的下调。在这些 miRNA 中，miR-21 因其在乳腺癌和许多其他癌症中的转录上调而闻名。总之，我们在这里描述的 HNRNPA1 的癌症特异性异构体转换强调了需要在癌症中研究异构体水平的基因表达，以确定新的致癌基因激活病例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/7e747dca1aa1/41598_2021_4007_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/ad11b3325643/41598_2021_4007_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/a2712567e57d/41598_2021_4007_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/7e747dca1aa1/41598_2021_4007_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/ad11b3325643/41598_2021_4007_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/b16b65bd14ef/41598_2021_4007_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/35491e468513/41598_2021_4007_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5176/8712528/7e747dca1aa1/41598_2021_4007_Fig7_HTML.jpg

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