The autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) induces senescence or quiescence of prostate, breast and liver cancer cells via transcriptional activation of p53

Tam, Chun W.; Liu, Vincent Wing Sun; Leung, Wai Ying; Yao, KM; Shiu, Stephen Y. W.

doi:10.1016/j.canlet.2008.05.047

Cited by 22 publications

(19 citation statements)

References 63 publications

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“…FABP5 promotes cell proliferation (19), and NID1 is a membrane glycoprotein providing a bridge between collagen 4 and laminin with a potential role in tissue recovery (4). PDZD2 is a secreted protein and also a tumor suppressor (52,53), and it may represent a novel myokine. SASH1 is a candidate tumor suppressor gene (46).…”

Section: Continuedmentioning

confidence: 99%

A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype

Keller

Vollaard

Gustafsson

et al. 2011

Journal of Applied Physiology

214

218

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The molecular pathways that are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ∼800 gene transcripts are regulated following 6 wk of supervised endurance training in young sedentary males, referred to as the training-responsive transcriptome (TRT) (Timmons JA et al. J Appl Physiol 108: 1487-1496, 2010). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as overrepresented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9, and PAX3 were downregulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, proangiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA-level validation there were several DNA variants that associated with maximal aerobic capacity (Vo(₂max)) trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption.

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Section: Continuedmentioning

confidence: 99%

A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype

Keller

Vollaard

Gustafsson

et al. 2011

Journal of Applied Physiology

214

218

View full text Add to dashboard Cite

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“…SOX4 has been shown to act as an oncogene in several cancers and may be the target gene of a frequently found amplification at 6p in lung cancer (Andersen et al, 2009;Medina et al, 2009). DLC1 (deleted in liver cancer 1) is frequently deleted in several solid cancers and PDZD2 has been shown to possess TS properties (Tam et al, 2008).…”

Section: Lung Cancer Associated Mirnas and Target Genes And Their Pomentioning

confidence: 99%

Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos‐ and histology‐related changes in lung cancer

Nymark

Guled

Borze

et al. 2011

Genes Chromosomes & Cancer

119

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Lung cancer has the highest mortality rate of all of the cancers in the world and asbestos-related lung cancer is one of the leading occupational cancers. The identification of asbestos-related molecular changes has long been a topic of increasing research interest. The aim of this study was to identify novel asbestos-related molecular correlates by integrating miRNA expression profiling with previously obtained profiling data (aCGH and mRNA expression) from the same patient material. miRNA profiling was performed on 26 tumor and corresponding normal lung tissue samples from highly asbestos-exposed and non-exposed patients, and on eight control lung tissue samples. Data analyses on miRNA expression, and integration of miRNA and previously obtained mRNA data were performed using Chipster. A separate analysis was used to integrate miRNA and previously obtained aCGH data. Both known and new lung cancer-associated miRNAs and target genes with inverse correlation were discovered. Furthermore, DNA copy number alterations (e.g., gain at 12p13.31) were correlated with the deregulated miRNAs. Specifically, thirteen novel asbestos-related miRNAs (over-expressed: miR-148b, miR-374a, miR-24-1*, Let-7d, Let-7e, miR-199b-5p, miR-331-3p, and miR-96 and under-expressed: miR-939, miR-671-5p, miR-605, miR-1224-5p and miR-202) and inversely correlated target genes (e.g., GADD45A, LTBP1, FOSB, NCALD, CACNA2D2, MTSS1, EPB41L3) were identified. In addition, over-expression of the well known squamous cell carcinoma-associated miR-205 was linked to down-regulation of the DOK4 gene. The miRNAs/genes presented here may represent interesting targets for further investigation and could eventually have potential diagnostic implications.

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“…GADD45A is involved in growth arrest through p53-dependent and independent mechanisms (47,48) and can interact via CDKN1A (49). PDZD2 is a tumour suppressor gene, reported to activate p53 by transcriptional regulation (50). RREB1 has an effect on p53 by binding to its promotor and transactivates its expression (51).…”

Section: à5mentioning

confidence: 99%

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

et al. 2017

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Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

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The autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) induces senescence or quiescence of prostate, breast and liver cancer cells via transcriptional activation of p53

Cited by 22 publications

References 63 publications

A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype

A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype

Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos‐ and histology‐related changes in lung cancer

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

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