Biopathological Significance of PIWI–piRNA Pathway Deregulation in Invasive Breast Carcinomas

Cancers

Thierry Dubois¹  Marick Laé²  Sabah Boudjemaa³  André Nicolas⁴  Renaud Leclere⁴  Gabriel Champenois⁴  Laetitia Lesage⁴  Walid Chemlali⁵  Sophie Vacher⁵  Anne Schnitzler⁵  Ivan Bieche⁵  Didier Meseure⁵ 

[1] Breast Cancer Biology Group, Translational Research Department, Institut Curie, Université PSL, 75005 Paris, France;Department of Pathology, Centre Henri Becquerel, INSERM U1245 UniRouen Normandie Université, rue d’Amiens, 76000 Rouen, France;Department of Pathology, Hôpital Armand Trousseau, 75012 Paris, France;Platform of Experimental Pathology PATHEX, Institut Curie, 75005 Paris, France;Unit of Pharmacogenomics, Department of Genetics, Institut Curie, 75005 Paris, France;

关键词: piRNA;    PIWI proteins;    transposable elements;    silencing;    methylation;    heterochromatin;   

DOI  :  10.3390/cancers12102833

来源: DOAJ

【 摘 要 】

The PIWI proteins emerging in the development of human cancers, edify PIWI-piRNA ribonucleoproteic complexes acting as pivotal regulators of genome integrity, differentiation and homeostasis. The aim of this study is to analyze the four PIWILs gene expression in invasive breast carcinomas (IBCs): at RNA level using quantitative RT-PCR (n = 526) and protein level using immunohistochemistry (n = 150). In normal breast tissue, PIWILs 2 and 4 were solely expressed, whereas an abnormal emergence of PIWIL1 and 3 was observed in respectively 30% and 6% of IBCs. Conversely, PIWIL2 was underexpressed in 48.3% and PIWIL4 downregulated in 43.3% of IBCs. Significant positive associations were observed between PIWIL4 underexpression, HR+ status and HR+ ERBB2+ molecular subtype and PIWIL2 underexpression, PR- status, ERBB2- status and molecular subtype. Similar patterns of PIWIL deregulation were observed in a multitumoral panel, suggesting a generic mechanism in most cancers. PIWIL2-4 underexpression was mainly regulated at epigenetic or post-transcriptional levels. PIWIL2 underexpression was significantly associated with DNA methylation and strong cytotoxic immune response. PIWIL2-4 were mainly associated with genes implicated in cell proliferation. As a result of this study, characterization of the PIWIL-piRNA pathway in IBCs opens interesting therapeutic perspectives using piRNAs, hypomethylating drugs, checkpoints immunotherapies and anti-PIWIL 1–3 antibodies.

【 授权许可】

Unknown