Prognostic and diagnostic relevance of hnRNP A2/B1, hnRNP B1 and S100 A2 in non-small cell lung cancer

Zech, Veronika F.E.; Dlaska, Margit; Tzankov, Alexandar; Hilbe, Wolfgang

doi:10.1016/j.cdp.2006.04.009

Cited by 35 publications

(26 citation statements)

References 28 publications

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“…HnRNP B1, an isoform of a broadly acting family of proteins, interacts with HOTAIR to contribute to the regulation of gene silencing and metastatic potential in breast cancer cells. The B1 isoform is frequently overexpressed in breast, lung, and hepatocellular carcinomas, and can serve as an important diagnostic and prognostic parameter (Sueoka et al 1999;Zhou et al 2001;Zech et al 2006;Cui et al 2010). Our work reveals a key role for A2/B1 in HOTAIR-mediated heterochromatin formation that promotes cell invasion.…”

Section: Hnrnp B1 As a New Regulator Of Hotairmentioning

confidence: 59%

An RNA matchmaker protein regulates the activity of the long noncoding RNA HOTAIR

Meredith

Balas

Sindy

et al. 2016

RNA

110

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The human long noncoding RNA (lncRNA) HOTAIR acts in trans to recruit the Polycomb repressive complex 2 (PRC2) to the HOXD gene cluster and to promote gene silencing during development. In breast cancers, overexpression of HOTAIR increases metastatic potential via the repression of many additional genes. It has remained unclear what factors determine HOTAIR-dependent PRC2 activity at specific genomic loci, particularly when high levels of HOTAIR result in aberrant gene silencing. To identify additional proteins that contribute to the specific action of HOTAIR, we performed a quantitative proteomic analysis of the HOTAIR interactome. We found that the most specific interaction was between HOTAIR and the heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, a member of a family of proteins involved in nascent mRNA processing and RNA matchmaking. Our data suggest that A2/B1 are key contributors to HOTAIR-mediated chromatin regulation in breast cancer cells: A2/B1 knockdown reduces HOTAIR-dependent breast cancer cell invasion and decreases PRC2 activity at the majority of HOTAIR-dependent loci. We found that the B1 isoform, which differs from A2 by 12 additional amino acids, binds with highest specificity to HOTAIR. B1 also binds chromatin and associates preferentially with RNA transcripts of HOTAIR gene targets. We furthermore demonstrate a direct RNA-RNA interaction between HOTAIR and a target transcript that is enhanced by B1 binding. Together, these results suggest a model in which B1 matches HOTAIR with transcripts of target genes on chromatin, leading to repression by PRC2.

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Section: Hnrnp B1 As a New Regulator Of Hotairmentioning

confidence: 59%

An RNA matchmaker protein regulates the activity of the long noncoding RNA HOTAIR

Meredith

Balas

Sindy

et al. 2016

RNA

110

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“…Likewise S100-A2, which shows overexpression in HNSCC, is also known to be overexpressed in other forms of cancer, such as non-small cell lung cancer and uterine leiomyoma (57,58). It has been demonstrated that calgizzarin plays an antiapoptotic role in an uterine leiomyosarcoma cell line (58).…”

Section: Discussionmentioning

confidence: 99%

Discovery and Verification of Head-and-neck Cancer Biomarkers by Differential Protein Expression Analysis Using iTRAQ Labeling, Multidimensional Liquid Chromatography, and Tandem Mass Spectrometry

Ralhan

DeSouza

Matta

et al. 2008

Molecular & Cellular Proteomics

204

216

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Multidimensional LC-MS/MS has been used for the analysis of biological samples labeled with isobaric mass tags for relative and absolute quantitation (iTRAQ) to identify proteins that are differentially expressed in human headand-neck squamous cell carcinomas (HNSCCs) in relation to non-cancerous head-and-neck tissues (controls) for cancer biomarker discovery. Fifteen individual samples (cancer and non-cancerous tissues) were compared against a pooled non-cancerous control (prepared by pooling equal amounts of proteins from six non-cancerous tissues) in five sets by on-line and off-line separation. We identified 811 non-redundant proteins in HNSCCs, including structural proteins, signaling components, enzymes, receptors, transcription factors, and chaperones. A panel of proteins showing consistent differential expression in HNSCC relative to the non-cancerous controls was discovered. Some of the proteins include stratifin (14-3-3); YWHAZ (14-3-3); three calcium-binding proteins of the S100 family, S100-A2, S100-A7 (psoriasin), and S100-A11 (calgizarrin); prothymosin ␣ (PTHA); L-lactate dehydrogenase A chain; glutathione S-transferase Pi; APC-binding protein EB1; and fascin. Peroxiredoxin2, carbonic anhydrase I, flavin reductase, histone H3, and polybromo-1D (BAF180) were underexpressed in HNSCCs. A panel of the three best performing biomarkers, YWHAZ, stratifin, and S100-A7, achieved a sensitivity of 0.92 and a specificity of 0.91 in discriminating cancerous from non-cancerous head-and-neck tissues. Verification of differential expression of YWHAZ, stratifin, and S100-A7 proteins in clinical samples of HNSCCs and paired and nonpaired non-cancerous tissues by immunohistochemistry, immunoblotting, and RT-PCR confirmed their overexpression in head-and-neck cancer. Verification of YWHAZ, stratifin, and S100-A7 in an independent set of HNSCCs achieved a sensitivity of 0.92 and a specificity of 0.87 in discriminating cancerous from non-cancerous head-andneck tissues, thereby confirming their overexpressions and utility as credible cancer biomarkers.

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“…High expression of S100A2 is associated with metastasis and predicts survival in early stages of NSCLC. These findings are supported by studies in a mouse model of non-small cell lung cancer (NSCLC) where NOD/SCID mice xenografted with NSCLC cells overexpressing S100A2 demonstrated significantly more metastases than vector alone transfected cells (Heighway et al, 2002;Diederichs et al, 2004;Smith et al, 2004;Wang et al, 2005;Zech et al, 2006;Bartling et al, 2007;Bulk et al, 2009;Strazisar et al, 2009a;Strazisar et al, 2009b).…”

Section: Notementioning

confidence: 86%

S100A2 (S100 calcium binding protein A2)

Scarlett¹,

Biankin²

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Prognostic and diagnostic relevance of hnRNP A2/B1, hnRNP B1 and S100 A2 in non-small cell lung cancer

Cited by 35 publications

References 28 publications

An RNA matchmaker protein regulates the activity of the long noncoding RNA HOTAIR

An RNA matchmaker protein regulates the activity of the long noncoding RNA HOTAIR

Discovery and Verification of Head-and-neck Cancer Biomarkers by Differential Protein Expression Analysis Using iTRAQ Labeling, Multidimensional Liquid Chromatography, and Tandem Mass Spectrometry

S100A2 (S100 calcium binding protein A2)

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