VILIP-1 Downregulation in Non-Small Cell Lung Carcinomas: Mechanisms and Prediction of Survival

Fu, Junjiang; Fong, K. M.; Bellacosa, Alfonso; Ross, Eric A.; Apostolou, Sinoula; Bassi, Daniel E.; Jin, Fang; Zhang, Jirong; Cairns, Paul; Cáceres, Inmaculada Ibáñez de; Braunewell, Karl-Heinz; Klein‐Szanto, Andres J.

doi:10.1371/journal.pone.0001698

Cited by 30 publications

(37 citation statements)

References 35 publications

(52 reference statements)

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“…Similarly, VILIP-1 expression is present in normal squamous epithelium of esophagus and bronchial mucociliary epithelium. Conversely VILIP-1 was down-regulated in squamous cell carcinomas from these two sites (10,11). Despite the recent reports that highlight the role of VILIP-1 in physiological and pathological processes, the molecular mechanisms controlling its expression remain unknown.…”

Section: Vilip-1mentioning

confidence: 94%

“…Recently, we reported the cloning of a 2-kb VSNL1 promoter from the 5Ј-untranslated region of the gene (11). The VSNL1 2-kb promoter contains two CpG islands that are the targets of methylation modification, constituting one of the epigenetic mechanisms contributing to the silencing of VSNL1 gene expression in lung and other cancer cells.…”

Section: Vilip-1mentioning

confidence: 99%

“…The VSNL1 2-kb promoter contains two CpG islands that are the targets of methylation modification, constituting one of the epigenetic mechanisms contributing to the silencing of VSNL1 gene expression in lung and other cancer cells. Increased acetylation of histones 3 and 4 around the VSNL1 promoter by the histone deacetylase inhibitor, trichostatin A, released the inhibition of gene expression, thus leading to the reactivation of VSNL1 expression (11). To further understand VSNL1 gene regulation and identify the transcriptional elements of the human VSNL1 promoter, we characterized the 2-kb VSNL1 promoter by deletion, mutation, and in vitro DNA binding and chromatin immunoprecipitation assays.…”

Section: Vilip-1mentioning

confidence: 99%

“…After the cross-linking was reversed by heating the sample at 65°C for 4 h, DNA was then extracted with phenol/chloroform and precipitated with ethanol. PCR was performed by using 1% of immunoprecipitated material and the same primers as used before (11). The following PCR program was used: 95°C for 5 min followed by 35-40 cycles of 95°C for 35 s, 54°C for 45 s, 72°C for 40 s, and finally 72°C for 10 min.…”

Section: Gcaggcmentioning

confidence: 99%

“…Methylation of VSNL1 Promoter-The promoter-specific methylation of VSNL1 was performed according to a published protocol (11). In this case we used HhaI DNA methyltransferase (New England Biolabs, Ipswich, MA) in the methylationmodifying treatment.…”

Section: Gcaggcmentioning

confidence: 99%

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Promoter Regulation of the Visinin-like Subfamily of Neuronal Calcium Sensor Proteins by Nuclear Respiratory Factor-1

Zhang

Jin

et al. 2009

Journal of Biological Chemistry

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VILIP-1 (gene name VSNL1), a member of the neuronal Ca 2؉sensor protein family, acts as a tumor suppressor gene by inhibiting cell proliferation, adhesion, and invasiveness. VILIP-1 expression is down-regulated in several types of human cancer. In human non-small cell lung cancer, we found that down-regulation was due to epigenetic changes. Consequently, in this study we analyzed the VSNL1 promoter and its regulation. Serial truncation of the proximal 2-kb VSNL1 promoter (VP-1998) from its 5 terminus disclosed that the last 3 terminal 100-bp promoter fragment maintained similar promoter activity as compared with VP-1998 and therefore was referred to as VSNL1 minimal promoter. When the 5 terminal 50 bp were deleted from the minimal promoter, the activity was dramatically decreased, suggesting that the deleted 50 bp contained a potential cis-acting element crucial for promoter activity. Deletion and site-directed mutagenesis combined with in silico transcription factor binding analysis of VSNL1 promoter identified nuclear respiratory factor (NRF)-1/␣-PAL as a major player in regulating VSNL1 minimal promoter activity. The function of NRF-1 was further confirmed using dominant-negative NRF-1 overexpression and NRF-1 small interfering RNA knockdown. Electrophoretic mobility shift assay and chromatin immunoprecipitation provided evidence for direct NRF-1 binding to the VSNL1 promoter. Methylation of the NRF-1-binding site was found to be able to regulate VSNL1 promoter activity. Our results further indicated that NRF-1 could be a regulatory factor for gene expression of the other visininlike subfamily members including HPCAL4, HPCAL1, HPCA, and NCALD.

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Section: Vilip-1mentioning

confidence: 94%

Section: Vilip-1mentioning

confidence: 99%

Section: Vilip-1mentioning

confidence: 99%

Section: Gcaggcmentioning

confidence: 99%

Section: Gcaggcmentioning

confidence: 99%

See 3 more Smart Citations

Promoter Regulation of the Visinin-like Subfamily of Neuronal Calcium Sensor Proteins by Nuclear Respiratory Factor-1

Zhang

Jin

et al. 2009

Journal of Biological Chemistry

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A transcriptional network signature characterizes lung cancer subtypes

Chang

Dreyfuss

Ramoni

2010

Cancer

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BACKGROUND: Transcriptional networks play a central role in cancer development. The authors described a systems biology approach to cancer classification based on the reverse engineering of the transcriptional network surrounding the 2 most common types of lung cancer: adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS: A transcriptional network classifier was inferred from the molecular profiles of 111 human lung carcinomas. The authors tested its classification accuracy in 7 independent cohorts, for a total of 422 subjects of Caucasian, African, and Asian descent. RESULTS: The model for distinguishing AC from SCC was a 25-gene network signature. Its performance on the 7 independent cohorts achieved 95.2% classification accuracy. Even more surprisingly, 95% of this accuracy was explained by the interplay of 3 genes (KRT6A, KRT6B, KRT6C) on a narrow cytoband of chromosome 12. The role of this chromosomal region in distinguishing AC and SCC was further confirmed by the analysis of another group of 28 independent subjects assayed by DNA copy number changes. The copy number variations of bands 12q12, 12q13, and 12q12-13 discriminated these samples with 84% accuracy. CONCLUSIONS: These results suggest the existence of a robust signature localized in a relatively small area of the genome, and show the clinical potential of reverse engineering transcriptional networks from molecular profiles. Cancer 2011;117:353-60.

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Involvement of VILIP‐1 (visinin‐like protein) and opposite roles of cyclic AMP and GMP signaling in in vitro cell migration of murine skin squamous cell carcinoma

Schönrath

Pan

Klein‐Szanto

et al. 2010

Molecular Carcinogenesis

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VILIP-1 (visinin-like protein 1) is downregulated in various human squamous cell carcinoma. In a mouse skin SCC model VILIP-1 expression is reduced in aggressive tumor cells, accompanied by reduced cAMP levels. Overexpression of VILIP-1 in aggressive SCC cells led to enhanced cAMP production, in turn causing a reduction in invasive properties. Moreover, in primary neurons and neuronal tumor lines VILIP-1 enhanced cGMP-signaling. Here, we set out to determine whether and how cAMP and cGMP-signaling contribute to the VILIP-1 effect on enhanced SCC model cell migration, and thus most likely invasiveness in vivo. We found stronger increase in cGMP levels in aggressive, VILIP-1-negative SCC cells following stimulation of guanylyl cyclases NPR-A and -B with the natriuretic peptides ANP and CNP, respectively. Incubation with ANP or 8Br-cGMP to increase cGMP levels further enhanced the migration capacity of aggressive cells, whereas cell adhesion was unaffected. Increased cGMP was caused by elevated expression levels of NPR-A and NPR-B. However, the expression level of VILIP-1 did not affect cGMP signaling and guanylyl cyclase expression in SCC. In contrast, VILIP-1 led to reduced migration of aggressive SCC cells depending on cAMP levels as shown by use of adenylyl cyclase inhibitor 2′,3′-dideoxyadenosine. Involvement of cAMP-effectors PKA and EPAC play a role downstream of adenylyl cyclase activation. VILIP-1-positive and -negative cells did not differ in mRNA expression of adenylyl cyclases, but an effect on enhanced protein expression and membrane localization of ACs was shown to underlie enhancement of cAMP production and, thus, reduction in cell migration by VILIP-1.

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VILIP-1 Downregulation in Non-Small Cell Lung Carcinomas: Mechanisms and Prediction of Survival

Cited by 30 publications

References 35 publications

Promoter Regulation of the Visinin-like Subfamily of Neuronal Calcium Sensor Proteins by Nuclear Respiratory Factor-1

Promoter Regulation of the Visinin-like Subfamily of Neuronal Calcium Sensor Proteins by Nuclear Respiratory Factor-1

A transcriptional network signature characterizes lung cancer subtypes

Involvement of VILIP‐1 (visinin‐like protein) and opposite roles of cyclic AMP and GMP signaling in in vitro cell migration of murine skin squamous cell carcinoma

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