Heterogeneous nuclear ribonucleoprotein <scp>A2</scp>/<scp>B1</scp> in association with <scp>hTERT</scp> is a potential biomarker for hepatocellular carcinoma

Mizuno, Hideki; Honda, Masao; Shirasaki, Takayoshi; Yamashita, Taro; Mizukoshi, Eishiro; Kaneko, Shuichi

doi:10.1111/j.1478-3231.2012.02778.x

Cited by 27 publications

(22 citation statements)

References 37 publications

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“…As shown in Figure 7A, direct interaction between hnRNPA2/B1 and p300 were observed in A549, H1299 and H460 cell lines by immunoprecipitation experiments. To further confirm the interaction between p300 and hnRNPA2/B1, we also analyzed the subcellular co-localization of p300 and hnRNPA2/B1 in H460, H322, H1299 cells by immunofluorescence confocal assay, and found that most of hnRNPA2/B1 and p300 proteins colocalized in the cell nuclei of H460 cells ( Figure 7B) and H322, H1299 cells ( Supplementary Figure 4), which are consistent with the previous study (Mizuno et al, 2012).…”

Section: Hnrnpa2/b1 Expression Was Positively Correlated With Cox-2 Esupporting

confidence: 90%

hnRNPA2/B1 activates cyclooxygenase‐2 and promotes tumor growth in human lung cancers

et al. 2015

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Cyclooxygenase-2 (COX-2) is highly expressed in tumor cells and has been regarded as a hallmarker for cancers, but the excise regulatory mechanism of COX-2 in tumorigenesis remains largely unknown. Here, we pulled down and identified a novel COX-2 regulator, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), which could specifically bind to COX-2 core promoter and regulate tumor growth in non-small-cell lung cancers (NSCLCs). Knockdown of hnRNPA2/B1 by shRNA or siRNA downregulated COX-2 expression and prostaglandin E2 (PGE 2 ) production, and suppressed tumor cell growth in NSCLC cells in vitro and in vivo. Conversely, overexpression of hnRNPA2/B1 up-regulated the levels of COX-2 and PGE 2 and promoted tumor cell growth. We also showed that hnRNPA2/B1 expression was positively correlated with COX-2 expression in NSCLC cell lines and tumor tissues, and the up-regulated expression of hnRNPA2/B1 and COX-2 predicted worse prognosis in NSCLC patients. Furthermore, we demonstrated that the activation of COX-2 expression by hnRNPA2/B1 was mediated through the cooperation with p300, a transcriptional co-activator, in NSCLC cells. The hnRNPA2/B1 could interact with p300 directly and be acetylated by p300. Exogenous overexpression of p300, but not its histone acetyltransferase (HAT) domain deletion mutation, augmented the acetylation of hnRNPA2/B1 and enhanced its binding on COX-2 promoter, thereby promoted COX-2 expression and lung cancer cell growth. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor

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Section: Hnrnpa2/b1 Expression Was Positively Correlated With Cox-2 Esupporting

confidence: 90%

hnRNPA2/B1 activates cyclooxygenase‐2 and promotes tumor growth in human lung cancers

et al. 2015

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“…Its cytoplasmic localization is considered a bona fide biomarker of hepatocellular carcinoma 42,43 or lung cancer. 40,41 This could explain why HNRNPA2B1 is functionally relevant for the studied oncogenic features in PDAC cells with a higher cytoplasmic distribution of this protein (KRASdependent PDAC) rather than for the HNRNPA2B1-nuclear-confined KRAS-independent PDAC (Fig 2 and 3).…”

Section: Discussionmentioning

confidence: 99%

“…We identified 6 specific proteins (Fig S1). We focused on heterogeneous nuclear ribonucleoprotein A2/B1 (hereinafter referred to as HNRNPA2B1) (Mowse score= 3.89e+005; sequence coverage =35 %; peptides matched= 10/108) given the described involvement of its cytoplasmic accumulation in malignancies harboring oncogenic KRAS [40][41][42][43] In order to confirm and further characterize the interaction, co-immunoprecipitation with the active form of the major RAS isoforms was studied. We observed a specific interaction with the K-and N-RAS isoforms, being excluded from the H-RAS (Fig 1A).…”

Section: Identification Of Hnrnpa2b1 As a Novel Oncogenic Kras Interamentioning

confidence: 99%

Ribonucleoprotein HNRNPA2B1 Interacts With and Regulates Oncogenic KRAS in Pancreatic Ductal Adenocarcinoma Cells

et al. 2014

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“…HnRNPA2 colocalizes with telomeric chromatin in the subset of PML bodies that are a hallmark of ALT cells, reinforcing the evidence for hnRNPs having a role in telomere maintenance. HnRNP A2/B1 was recently shown to be associated with human telomerase reverse transcriptase (hTERT) and increase telomerase activity in hepatocellular carcinoma which is a new prognostic biomarker (Mizuno, Honda et al 2012). We therefore believe mitochondrial retrograde signaling induced activation of hnRNPA2 which is a telomere regulatory protein is a possible epigenetic link between mitochondrial functional state and nuclear gene expression and telomere state.…”

Section: Mitochondrial Retrograde Signaling As An Epigenetic Regulmentioning

confidence: 99%

Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics

2013

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Mitochondria play a central role not only in energy production but also in the integration of metabolic pathways as well as signals for apoptosis and autophagy. It is becoming increasingly apparent that mitochondria in mammalian cells play critical roles in the initiation and propagation of various signaling cascades. In particular, mitochondrial metabolic and respiratory states and status on mitochondrial genetic instability are communicated to the nucleus as an adaptive response through retrograde signaling. Each mammalian cell contains multiple copies of mitochondrial genome (mtDNA). A reduction in mtDNA copy number has been reported in various human pathological conditions such as diabetes, obesity, neurodegenerative disorders, aging and cancer. Reduction in mtDNA copy number disrupts mitochondrial membrane potential (Δψm) resulting in dysfunctional mitochondria. Dysfunctional mitochondria trigger retrograde signaling and communicate their changing metabolic and functional state to the nucleus as an adaptive response resulting in altered nuclear gene expression profile and altered cell physiology and morphology. In this review, we provide an overview of the various modes of mitochondrial retrograde signaling focusing particularly on the Ca2+/Calcineurin mediated retrograde signaling. We discuss the contribution of the key factors of the pathway such as Calcineurin, IGF1 receptor, Akt kinase and HnRNPA2 in the propagation of signaling and their role in modulating genetic and epigenetic changes favoring cellular reprogramming towards tumorigenesis.

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Heterogeneous nuclear ribonucleoprotein A2/B1 in association with hTERT is a potential biomarker for hepatocellular carcinoma

Abstract: Heterogeneous nuclear ribonucleoprotein A2/B1, an hTERT-associated protein, is a potential prognostic biomarker for HCC patients and might be a therapeutic target of HCC.

Cited by 27 publications

References 37 publications

hnRNPA2/B1 activates cyclooxygenase‐2 and promotes tumor growth in human lung cancers

hnRNPA2/B1 activates cyclooxygenase‐2 and promotes tumor growth in human lung cancers

Ribonucleoprotein HNRNPA2B1 Interacts With and Regulates Oncogenic KRAS in Pancreatic Ductal Adenocarcinoma Cells

Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics

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