Immunoexpression Analysis and Prognostic Value of BLCAP in Breast Cancer

Gromova, Irina; Gromov, Pavel; Kroman, Niels; Wielenga, Vera Timmermans; Simon, Ronald; Sauter, Guido; Moreira, José M.A.

doi:10.1371/journal.pone.0045967

Cited by 9 publications

(6 citation statements)

References 41 publications

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“…Among these 10 genes, PAK3 and IL15RA were previously shown to be involved in PCa progression [ 52 , 53 ], and PAK3 was identified as an epigenetic biomarker for the prognostic diagnosis of PCa [ 52 ]. Despite the fact that no reports on the association of the remaining genes with PCa were found, these genes were shown to be associated with the progression of other cancers, such as breast cancer [ 54 ] pancreatic cancer [ 55 ] and leukemia [ 56 ]. These evidences support that miR-648 could be involved in PCa and act as a novel molecular biomarker for PCa diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate miRNA biomarkers from miRNA regulatory network with application to prostate cancer

et al. 2014

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BackgroundMicroRNAs (miRNAs) are a class of non-coding regulatory RNAs approximately 22 nucleotides in length that play a role in a wide range of biological processes. Abnormal miRNA function has been implicated in various human cancers including prostate cancer (PCa). Altered miRNA expression may serve as a biomarker for cancer diagnosis and treatment. However, limited data are available on the role of cancer-specific miRNAs. Integrative computational bioinformatics approaches are effective for the detection of potential outlier miRNAs in cancer.MethodsThe human miRNA-mRNA target network was reconstructed by integrating multiple miRNA-mRNA interaction datasets. Paired miRNA and mRNA expression profiling data in PCa versus benign prostate tissue samples were used as another source of information. These datasets were analyzed with an integrated bioinformatics framework to identify potential PCa miRNA signatures. In vitro q-PCR experiments and further systematic analysis were used to validate these prediction results.ResultsUsing this bioinformatics framework, we identified 39 miRNAs as potential PCa miRNA signatures. Among these miRNAs, 20 had previously been identified as PCa aberrant miRNAs by low-throughput methods, and 16 were shown to be deregulated in other cancers. In vitro q-PCR experiments verified the accuracy of these predictions. miR-648 was identified as a novel candidate PCa miRNA biomarker. Further functional and pathway enrichment analysis confirmed the association of the identified miRNAs with PCa progression.ConclusionsOur analysis revealed the scale-free features of the human miRNA-mRNA interaction network and showed the distinctive topological features of existing cancer miRNA biomarkers from previously published studies. A novel cancer miRNA biomarker prediction framework was designed based on these observations and applied to prostate cancer study. This method could be applied for miRNA biomarker prediction in other cancers.

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Section: Discussionmentioning

confidence: 99%

Identification of candidate miRNA biomarkers from miRNA regulatory network with application to prostate cancer

et al. 2014

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“…Tissue microarrays (TMAs) were purchased from Pantomics (BRC961, BRC962 BRC1501, BRC1502, BRC1503), Richmond, CA, USA). Additional tissue samples of normal breast tissue were produced and processed as previously published 57 . FFPE cell-blocks were prepared as in Cabezon et al 58 .…”

Section: Methodsmentioning

confidence: 99%

Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1

et al. 2018

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Cancer cells utilize lysosomes for invasion and metastasis. Myeloid Zinc Finger1 (MZF1) is an ErbB2-responsive transcription factor that promotes invasion of breast cancer cells via upregulation of lysosomal cathepsins B and L. Here we identify let-7 microRNA, a well-known tumor suppressor in breast cancer, as a direct negative regulator of MZF1. Analysis of primary breast cancer tissues reveals a gradual upregulation of MZF1 from normal breast epithelium to invasive ductal carcinoma and a negative correlation between several let-7 family members and MZF1 mRNA, suggesting that the inverse regulatory relationship between let-7 and MZF1 may play a role in the development of invasive breast cancer. Furthermore, we show that MZF1 regulates lysosome trafficking in ErbB2-positive breast cancer cells. In line with this, MZF1 depletion or let-7 expression inhibits invasion-promoting anterograde trafficking of lysosomes and invasion of ErbB2-expressing MCF7 spheres. The results presented here link MZF1 and let-7 to lysosomal processes in ErbB2-positive breast cancer cells that in non-cancerous cells have primarily been connected to the transcription factor EB. Identifying MZF1 and let-7 as regulators of lysosome distribution in invasive breast cancer cells, uncouples cancer-associated, invasion-promoting lysosomal alterations from normal lysosomal functions and thus opens up new possibilities for the therapeutic targeting of cancer lysosomes.

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“…Other researchers reported that overexpression of BLCAP induced cell growth inhibition and apoptosis, suggested that BLCAP may function as a potential tumor suppressor in carcinogenesis through regulating cell proliferation and survival [ 4 – 6 ]. In addition, BLCAP represented a negative correlation with tumor progression by comparing its expression pattern in different grades and stages of bladder cancer and breast cancer, suggesting that it might be of value as a biomarker and providing a new perspective for the clinical application of this protein [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer

Chen

Cai

et al. 2017

Oncotarget

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Bladder cancer-associated protein (BLCAP) gene is a highly conserved gene with tumor-suppressor function in different carcinomas. It is also a novel ADAR-mediated editing substrate undergoes multiple A-to-I RNA editing events. Although the anti-tumorigenic role of BLCAP has been examined in preliminarily studies, the relationship between BLCAP function and A-to-I RNA editing in cervical carcinogenesis still require further exploration. Herein, we analyzed the coding sequence of BLCAP transcripts in 35 paired cervical cancer samples using high-throughput sequencing. Of note, editing levels of three novel editing sites were statistically different between cancerous and adjacent cervical tissues, and editing of these three sites was closely correlated. Moreover, two editing sites of BLCAP coding region were mapped-in the key YXXQ motif which can bind to SH2 domain of STAT3. Further studies revealed that BLCAP interacted with signal transducer and activator of transcription 3 (STAT3) and inhibited its phosphorylation, while A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer cell lines. Our findings reveal that A-to-I RNA editing events alter the genetically coded amino acid in BLCAP YXXQ motif, which drive the progression of cervical carcinogenesis through regulating STAT3 signaling pathway.

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Immunoexpression Analysis and Prognostic Value of BLCAP in Breast Cancer

Cited by 9 publications

References 41 publications

Identification of candidate miRNA biomarkers from miRNA regulatory network with application to prostate cancer

Identification of candidate miRNA biomarkers from miRNA regulatory network with application to prostate cancer

Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1

A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer

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