CAPER, a novel regulator of human breast cancer progression

Mercier, Isabelle Le; Gonzales, Donna M.; Quann, Kevin; Pestell, Timothy G.; Molchansky, Alexander; Sotgia, Federica; Hulit, James; Gândara, Ricardo; Wang, Chenguang; Pestell, Richard G.; Lisanti, Michael P.; Jasmin, Jean-François

doi:10.4161/cc.28156

Cited by 28 publications

(40 citation statements)

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“…Table S5). SRSF6 amplifications were observed before in colon tumors 25 and RBM39 overexpression was linked before to breast cancer progression 26 . Table S6).…”

Section: Patterns Of Rbp Mutations and Copy-number Variation Across Tmentioning

confidence: 99%

Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks

Sebestyén

Singh

Miñana

et al. 2015

Preprint

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Alternative splicing is regulated by multiple RNA-binding proteins and influences the expression of most eukaryotic genes. However, the role of this process in human disease, and particularly in cancer, is only starting to be unveiled. We systematically analyzed mutation, copy number, and gene expression patterns of 1348 RNA-binding protein (RBP) genes in 11 solid tumor types, together with alternative splicing changes in these tumors and the enrichment of binding motifs in the alternatively spliced sequences. Our comprehensive study reveals widespread alterations in the expression of RBP genes, as well as novel mutations and copy number variations in association with multiple alternative splicing changes in cancer drivers and oncogenic pathways. Remarkably, the altered splicing patterns in several tumor types recapitulate those of undifferentiated cells. These patterns are predicted to be mainly controlled by MBNL1 and involve multiple cancer drivers, including the mitotic gene NUMA1. We show that NUMA1 alternative splicing induces enhanced cell proliferation and centrosome amplification in nontumorigenic mammary epithelial cells. Our study uncovers novel splicing networks that potentially contribute to cancer development and progression.

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“…Table S5). SRSF6 amplifications were observed before in colon tumors 25 and RBM39 overexpression was linked before to breast cancer progression 26 . Table S6).…”

Section: Patterns Of Rbp Mutations and Copy-number Variation Across Tmentioning

confidence: 99%

Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks

Sebestyén

Singh

Miñana

et al. 2015

Preprint

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“…RNA binding motif protein 39 (RBM39), a member of the U2AF65 protein family, is a splicing factor and transcriptional co-activator of AP-1/Jun and estrogen receptors [98,99]. Moreover, shRNA downregulation of RBM39 activity leads to decreased expression of cell-cycle progression regulators, inhibits protein synthesis, prevents the phosphorylation of c-Jun [100], and when complexed with TBX3 is necessary for preventing primary cell and mouse embryo senescence [101]. Interestingly, RBM39 mRNA expression is abundant in many immune system-associated cells raising the possibility that modern ZIKV isolates may target directing or indirectly immune related genes for alternative splicing by changing the splicing of RBM39 ( Figure 5H) [102].…”

Section: Discussionmentioning

confidence: 99%

Asian Zika virus isolate significantly changes the transcriptional profile and alternative RNA splicing events in a neuroblastoma cell line

Bonenfant

Meng

Shotwell

et al. 2019

Preprint

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Alternative splicing of pre-mRNAs expands a single genetic blueprint to encode multiple functionally diverse protein isoforms. Viruses have previously been shown to interact with, depend on, and alter host splicing machinery. The consequences however incited by viral infection on the global alternative slicing (AS) landscape are under appreciated. Here we investigated the transcriptional and alternative splicing profile of neuronal cells infected with a contemporary Puerto Rican Zika virus (ZIKV PR ) isolate, the prototypical Ugandan ZIKV (ZIKV MR ) isolate and dengue virus 2 (DENV2). Our analyses revealed that ZIKV PR induced significantly more differential changes in expressed genes compared to ZIKV MR or DENV2, despite all three viruses showing equivalent infectivity and viral RNA levels. Consistent with the transcriptional profile, ZIKV PR induced a higher number of alternative splicing events compared to ZIKV MR or DENV2, and gene ontology analyses highlighted alternative splicing changes in genes associated with mRNA splicing. All three viruses modulated alternative splicing with ZIKV PR having the largest impact on splicing. ZIKV alteration of the transcriptomic landscape during infection caused changes in cellular RNA homeostasis, which might dysregulate neurodevelopment and function leading to neuropathologies such as microcephaly and Guillain-Barré syndrome associated with the ZIKV infection. IntroductionZika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that is classified within the Flaviviridae family. Other notable flaviviruses include Dengue virus (DENV), Yellow Fever virus (YFV), West Nile virus (WNV) and Tick-borne encephalitis virus, all of which are primarily transmitted via the bite of an infected mosquito or tick [1]. Flavivirus infections rarely result in death and common symptoms include maculopapular rash, fever, and achy joints [2]. Until the early 2000s, only 13 confirmed ZIKV infections in humans were reported [3-6]. The first major outbreak of ZIKV occurred in 2007 on Yap Island [7], followed by a 2010 outbreak in Cambodia [8], and an outbreak in French Polynesia in 2013 which resulted in more than 29,000 human infections [9]. This Asian lineage of ZIKV expanded west and in 2015 efforts were redirected towards understanding the link between ZIKV infection and the associated neurological pathologies that are now termed Congenital Zika Syndrome (CZS) [10,11]. To date there are no antivirals or a licensed vaccine to prevent ZIKV infection. Therefore, to develop effective therapies and thus limit the dreadful symptoms associated with ZIKV infection it is critical to understand viral-host interactions and ZIKV pathogenesis.The striking feature of the recent ZIKV outbreak in the America's was the correlation between intrauterine ZIKV infection and the devastating consequences to fetal brain development resulting in microcephaly, cortical malformations and intracranial calcifications [12][13][14][15] and the increased number of cases of Guillain-Barré syndrome in adults [16][17][18][...

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“…PCNA DNA sentezi için özel, nükleer bir proteindir. Primer olarak nükleusta, hücre siklusunun S fazında ortaya çıkar [1,3,25]. Yüksek PCNA skoru kötü prognozun bir göstergesidir.…”

Section: Discussionunclassified

“…Heterojen ve progresif bir hastalık olan meme karsinomu kadınlarda görülen en sık malignite olup önemli mortalite sebeplerinden biridir [1][2][3][4][5][6]. Duktal karsinoma in situnun (DKİS) bir seri anormal hücresel değişikliğin artarak izlendiği, hiperplaziden atipik hiperplaziye, noninvaziv karsinomaya, invaziv karsinomaya ve son olarak metastatik karsinomaya giden bir spektrumda, normal epitelyal hücrelerden geliştiği varsayılmaktadır [7].…”

Section: Introductionunclassified

P53, HER2/neu, Bcl-2 and PCNA overexpression in ductal carcinoma in situ lesions of the breast and their role in progression to invasive carcinoma

Tad

Kulaçoğlu

2019

Ortadogu Tıp Derg

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To cite this article: Tad M, Kulaçoğlu S. Memenin duktal karsinoma in situ lezyonlarında P53, HER2/neu, Bcl-2 ve PCNA ekspresyonu ve bunların invaziv karsinoma progresyonda rolleri. Ortadogu Tıp Derg 2019; 11(4): 490-496. https://doi.org/10.21601/ortadogutipdergisi.536772 Orijinal Makale ___________________________________________________________ Memenin duktal karsinoma in situ lezyonlarında P53, HER2/neu, Bcl-2 ve PCNA ekspresyonu ve bunların invaziv karsinoma progresyonda rolleri P53, HER2/neu, Bcl-2 and PCNA overexpression in ductal carcinoma in situ lesions of the breast and their role in progression to invasive carcinoma ÖZ Amaç: Proliferatif aktivitenin, onkogenlerde ve tümör süpresör genlerdeki değişikliklerin anlaşılması, duktal karsinoma in situnun invaziv meme kanserine gelişme ihtimalinin yüksek olduğu olguları belirlemede önemli olabilir. Bu çalışmada p53, HER2/neu, bcl-2 ve PCNA overekspresyonunun duktal karsinoma in situnun progresyonu ile ilişkisi değerlendirildi. Gereç ve Yöntem:Biz 20 duktal karsinoma in situ (grup 1) ve 20 invaziv duktal karsinoma birlikteliğinde duktal karsinoma in situ (grup 2) olgusunu değerlendirdik. Olgulara immünhistokimyasal yöntemler kullanılarak p53, HER2/neu, bcl-2 ve PCNA çalışıldı.Bulgular: Grup 2 olgularında p53, HER2/neu ve PCNA overekspresyonu daha yüksekti. Ancak farklar istatistiksel olarak anlamlı değildi (p>0,05). Grup 1 olgularının %36,8'inde, grup 2 olgularının %70'inde bcl-2 overekspresyonu izlendi. İki grup arasındaki bu fark istatistiksel olarak anlamlıydı (p<0,05). Çalışmamızda önemli bulgulardan biri de, p53, HER2/neu, bcl-2 ve PCNA overekspresyonunun aynı anda grup 2 olgularının 3'ünde izlenirken grup 1 olgularının hiçbirinde gözlenmemesiydi.Sonuç: Bulgular bize, bcl-2 overekspresyonunun duktal karsinoma in situnun invaziv duktal karsinomaya gelişim ihtimalinin yüksek olduğu olguları belirlemede daha değerli olabileceğini, invaziv duktal karsinoma gelişiminde farklı progresyon yollarının varolduğunu, preinvaziv evrede bu değişikliklerin birden fazlasının aynı olguda tespit edilmesinin invaziv duktal karsinomaya progresyon riskini belirlemede tek başlarına olduğundan daha değerli olabileceğini gösterdi. Bu sonuçlar farklı biyolojik davranışa sahip DKIS alt tiplerinin tanımlanmasına katkı sağlayacaktır. Anahtar kelimeler: Duktal karsinoma in situ, p53, HER2/neu, bcl-2, PCNA Ortadoğu Tıp Dergisi / Ortadogu Medical Journal ORTADOGU MEDICAL JOURNAL 2019; 11(4): 490-496 491ABSTRACT Objective: Understanding proliferative activity and the changes in oncogenes and tumour supressor genes may be important to predict the ductal carsinoma in situ cases that have high probability of progression to invasive breast carcinoma. In this study the correlation between p53, HER2/neu, bcl-2 and PCNA overexpression and progression of ductal carsinoma in situ were evaluated. Methods:We evaluated 20 ductal carsinoma in situ (group 1) and 20 ductal carsinoma in situ associated with invasive ductal carcinoma cases (group 2). We studied p53, HER2/neu, bcl-2 ve PCNA to cases im...

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CAPER, a novel regulator of human breast cancer progression

Cited by 28 publications

References 50 publications

Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks

Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks

Asian Zika virus isolate significantly changes the transcriptional profile and alternative RNA splicing events in a neuroblastoma cell line

P53, HER2/neu, Bcl-2 and PCNA overexpression in ductal carcinoma in situ lesions of the breast and their role in progression to invasive carcinoma

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