Splicing regulator SLU7 preserves survival of hepatocellular carcinoma cells and other solid tumors via oncogenic miR-17-92 cluster expression.

Oncogene
R UrtasunC Berasain

Abstract

Resisting death is a central hallmark of cancer cells. Tumors rely on a number of genetic mechanisms to avoid apoptosis, and alterations in mRNA alternative splicing are increasingly recognized to have a role in tumorigenesis. In this study, we identify the splicing regulator SLU7 as an essential factor for the preservation of hepatocellular carcinoma (HCC) cells viability. Compared with hepatocytes, SLU7 expression is reduced in HCC cells; however, further SLU7 depletion triggered autophagy-related cellular apoptosis in association with the overproduction of reactive oxygen species. Remarkably, these responses were not observed in primary human hepatocytes or in the well-differentiated HepaRG cell line. Mechanistically, we demonstrate that SLU7 binds the C13orf25 primary transcript in which the polycistronic oncomir miR-17-92 cluster is encompassed, and is necessary for its processing and expression. SLU7 knockdown altered the splicing of the C13orf25 primary transcript, and markedly reduced the expression of its miR-17, miR-20 and miR-92a constituents. This led to the upregulation of CDKN1A (P21) and BCL2L11 (BIM) expression, two bona fide targets of the miR-17-92 cluster and recognized mediators of its pro-survival and tumor...Continue Reading

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Citations

Jun 19, 2017·Neoplasia : an International Journal for Oncology Research·Oguzhan BegikAyse Elif Erson-Bensan
Jan 19, 2019·Nucleic Acids Research·Maddalen JiménezCarmen Berasain
Oct 24, 2019·International Journal of Molecular Sciences·Po-Shuan HuangKwang-Huei Lin
May 26, 2018·Biological Reviews of the Cambridge Philosophical Society·Shama P KabekkoduKapaettu Satyamoorthy
May 1, 2021·Biomedicines·Lola Llobat, Olivia Gourbault
Aug 1, 2021·Nucleic Acids Research·Miriam RecaldeCarmen Berasain
Jun 26, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·María Gárate-RascónCarmen Berasain

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