Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues

Boukakis, Georgios; Patrinou-Georgoula, Meropi; Lekarakou, Maria; Valavanis, Christos; Guialis, Apostolia

doi:10.1186/1471-2407-10-434

Cited by 64 publications

(45 citation statements)

References 31 publications

(60 reference statements)

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“…Furthermore, previous studies from our laboratory and others demonstrated functional oncogenic roles for several splicing factors, including hnRNP A2/B1 (Karni et al 2007;Golan-Gerstl et al 2011;Lefave et al 2011;Cohen-Eliav et al 2013). Overexpression of hnRNP A1/A2 proteins has been reported in several cancers (Zhou et al 2001a(Zhou et al , 2013Ushigome et al 2005;Li et al 2009;Ma et al 2009;Boukakis et al 2010;Wang et al 2011). In HCC, the splicing factor SRSF1 has been shown to regulate splicing of tumor suppressors such as KLF-6 (Munoz et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

Shilo¹,

Hur²,

Denichenko³

et al. 2014

RNA

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In recent years, it has become clear that splicing factors play a direct role in cancer development. We showed previously that splicing factors SRSF1, SRSF6, and hnRNP A2/B1 are up-regulated in several cancers and can act as oncogenes when up-regulated. Here we examined the role of splicing factors hnRNP A1/A1b and hnRNP A2/B1 in hepatocellular carcinoma (HCC). We show that the splicing factors hnRNP A1 and hnRNP A2 are up-regulated in HCC tumors derived from inflammation-induced liver cancer mouse model. Overexpression of hnRNP A1 or hnRNP A2, but not the splicing isoform hnRNP B1, induced tumor formation of immortalized liver progenitor cells, while knockdown of these proteins inhibited anchorage-independent growth and tumor growth of human liver cancer cell lines. In addition, we found that cells overexpressing hnRNP A2 showed constitutive activation of the Ras-MAPK-ERK pathway. In contrast, knockdown of hnRNP A2 inhibited the Ras-MAPK-ERK pathway and prevented ERK1/2 activation by EGF. Moreover, we found that hnRNP A2 regulates the splicing of A-Raf, reducing the production of a short dominant-negative isoform of A-Raf and elevating the full-length A-Raf transcript. Taken together, our data suggest that hnRNP A2 up-regulation in HCC induces an alternative splicing switch that down-regulates a dominant-negative isoform of A-Raf, leading to activation of the Raf-MEK-ERK pathway and cellular transformation.

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Section: Discussionmentioning

confidence: 99%

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

Shilo¹,

Hur²,

Denichenko³

et al. 2014

RNA

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“…hnRNP A1 hnRNP A1 has been found to be deregulated in various types of cancers, including colon, 89 lung, 90 and liver, 91 usually leading to overexpression of hnRNP A1 mRNA and protein. Expression levels are correlated with increased proliferation 92,93 and tumor metabolism.…”

Section: The Oncogenic Activities Of Hnrnp Splicing Factorsmentioning

confidence: 99%

The role of splicing factors in deregulation of alternative splicing during oncogenesis and tumor progression

Shilo

Siegfried

Karni

2014

Molecular & Cellular Oncology

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In past decades, cancer research has focused on genetic alterations that are detected in malignant tissues and contribute to the initiation and progression of cancer. These changes include mutations, copy number variations, and translocations. However, it is becoming increasingly clear that epigenetic changes, including alternative splicing, play a major role in cancer development and progression. There are relatively few studies on the contribution of alternative splicing and the splicing factors that regulate this process to cancer development and progression. Recently, multiple studies have revealed altered splicing patterns in cancers and several splicing factors were found to contribute to tumor development. Studies using high-throughput genomic analysis have identified mutations in components of the core splicing machinery and in splicing factors in several cancers. In this review, we will highlight new findings on the role of alternative splicing and its regulators in cancer initiation and progression, in addition to novel approaches to correct oncogenic splicing.

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“…27 Numerous of researches indicate that HNRNPA2B1was involved in the tumorigenesis of pancreatic cancer, 28,29 prostate cancer, 30 hepatocellular carcinoma, 31 and LC. 32 Higher expression level of HNRNPA2B1 in tissues from patients with gastric adenocarcinoma, 33 non-small cell LC 34 and hepatocellular carcinoma 35 has been reported. The autoimmune responses to HNRNPA2B1 have been described previously in patients with hepatitis, 36 but not reported for cancer.…”

Section: Discussionmentioning

confidence: 98%

Identification of autoantibodies to ECH1 and HNRNPA2B1 as potential biomarkers in the early detection of lung cancer

Dai

Tsay

et al. 2017

OncoImmunology

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Identification of biomarkers for early detection of lung cancer (LC) is important, in turn leading to more effective treatment and reduction of mortality. Serological proteome analysis (SERPA) was used to identify proteins around 34 kD as ECH1 and HNRNPA2B1, which had been recognized by serum autoantibody from 25 LC patients. In the validation study, including 90 sera from LC patients and 89 sera from normal individuals, autoantibody to ECH1 achieved an area under the curve (AUC) of 0.799 with sensitivity of 62.2% and specificity of 95.5% in discriminating LC from normal individuals, and showed negative correlation with tumor size (r s D ¡0.256, p D 0.023). Autoantibody to HNRNPA2B1 performed an AUC of 0.874 with sensitivity of 72.2% and specificity of 95.5%, and showed negative correlation with lymph node metastasis (r s D ¡0.279, p D 0.012). By using longitudinal preclinical samples, autoantibody to ECH1 showed an AUC of 0.763 with sensitivity of 60.0% and specificity of 89.3% in distinguishing early stage LC from matched normal controls, and elevated autoantibody levels could be detected greater than 2 y before LC diagnosis. ECH1 and HNRNPA2B1 are autoantigens that elicit autoimmune responses in LC and their autoantibody can be the potential biomarkers for the early detection of LC.

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Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues

Cited by 64 publications

References 31 publications

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

The role of splicing factors in deregulation of alternative splicing during oncogenesis and tumor progression

Identification of autoantibodies to ECH1 and HNRNPA2B1 as potential biomarkers in the early detection of lung cancer

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