Genomic profiling screens small molecules of metastatic prostate carcinoma

Xu, Axiang; Sun, Shengkun

doi:10.3892/ol.2015.3472

Cited by 16 publications

(17 citation statements)

References 41 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, our data show that its expression is strongly associated with pathological stages and Gleason scores in human PCa samples, indicating the pro-malignance role of this nuclear importer. In support of this observation, recent genomic profiling screening also demonstrated the importance of KPNA4 during the process of prostate carcinoma (50). …”

Section: Discussionmentioning

confidence: 67%

Inhibition of KPNA4 attenuates prostate cancer metastasis

Yang

Wei

et al. 2016

Oncogene

View full text Add to dashboard Cite

Prostate cancer (PCa) is a common cancer in men. Although current treatments effectively palliate symptoms and prolong life, the metastatic PCa remains incurable. It is important to find biomarkers and targets to improve metastatic PCa diagnosis and treatment. Here, we report a novel correlation between karyopherin α4 (KPNA4) and PCa pathological stages. KPNA4 mediates the cytoplasm-to-nucleus translocation of transcription factors including NF-κB while its role in PCa was largely unknown. We find that knockdown of KPNA4 reduces cell migration in multiple PCa cell lines, suggesting a role of KPNA4 in PCa progression. Indeed, stable knockdown of KPNA4 significantly reduces PCa invasion and distant metastasis in mouse models. Functionally, KPNA4 alters tumor microenvironment in terms of macrophage polarization and osteoclastogenesis by modulating TNF-α and -β. Further, KPNA4 is proved as a direct target of miR-708, a tumor-suppressive miRNA. We disclose the role of miR-708-KPNA4-TNF axes in PCa metastasis and KPNA4’s potential as a novel biomarker for PCa metastasis.

show abstract

Section: Discussionmentioning

confidence: 67%

Inhibition of KPNA4 attenuates prostate cancer metastasis

Yang

Wei

et al. 2016

Oncogene

View full text Add to dashboard Cite

show abstract

“…We used PARADIGM, a network modeling approach that integrates multiple data types to infer alterations in biological pathway activity that contribute to a specific phenotype or cell state [ 19 ]. PARADIGM inferred from the molecular profiling data an Integrated Pathway Level (IPL) score for each node in a reference pathway curated from Reactome, BioCarta, and NCI Nature pathway resources [ 37 ]. A key feature of PARADIGM is that the IPL for each node reflects both the input data (e.g., gene expression and copy number) as well as the scores of neighboring nodes.…”

Section: Resultsmentioning

confidence: 99%

Integrative molecular network analysis identifies emergent enzalutamide resistance mechanisms in prostate cancer

et al. 2017

View full text Add to dashboard Cite

Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines. Gene networks associated with enzalutamide resistance were revealed by performing an integrative genomic analysis with the PAthway Representation and Analysis by Direct Reference on Graphical Models (PARADIGM) tool. Amongst the pathways enriched in the enzalutamide-resistant cells were those associated with MEK, EGFR, RAS, and NFKB. Functional validation studies of 64 genes identified 10 candidate genes whose suppression led to greater effects on cell viability in enzalutamide-resistant cells as compared to sensitive parental cells. Examination of a patient cohort demonstrated that several of our functionally-validated gene hits are deregulated in metastatic CRPC tumor samples, suggesting that they may be clinically relevant therapeutic targets for patients with enzalutamide-resistant CRPC. Altogether, our approach demonstrates the potential of integrative genomic analyses to clarify determinants of drug resistance and rational co-targeting strategies to overcome resistance.

show abstract

“…Microarray analysis was performed by an Affymetrix GeneChip Hybridization Oven 640 and Gene Array Scanner 3000. Microarray data analysis was performed by the R software platform (v.2.13.0) and the limma (linear regression model) package (Ritchie et al, 2015; Xu and Sun, 2015). Detected global gene expressions at each time point following sciatic nerves transection were compared with the control group.…”

Section: Methodsmentioning

confidence: 99%

Ingenuity Pathway Analysis of Gene Expression Profiles in Distal Nerve Stump following Nerve Injury: Insights into Wallerian Degeneration

2016

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Nerve injury is a common and difficult clinical problem worldwide with a high disability rate. Different from the central nervous system, the peripheral nervous system is able to regenerate after injury. Wallerian degeneration in the distal nerve stump contributes to the construction of a permissible microenvironment for peripheral nerve regeneration. To gain new molecular insights into Wallerian degeneration, this study aimed to identify differentially expressed genes and elucidate significantly involved pathways and cellular functions in the distal nerve stump following nerve injury. Microarray analysis showed that a few genes were differentially expressed at 0.5 and 1 h post nerve injury and later on a relatively larger number of genes were up-regulated or down-regulated. Ingenuity pathway analysis indicated that inflammation and immune response, cytokine signaling, cellular growth and movement, as well as tissue development and function were significantly activated following sciatic nerve injury. Notably, a cellular function highly related to nerve regeneration, which is called Nervous System Development and Function, was continuously activated from 4 days until 4 weeks post injury. Our results may provide further understanding of Wallerian degeneration from a genetic perspective, thus aiding the development of potential therapies for peripheral nerve injury.

show abstract

Genomic profiling screens small molecules of metastatic prostate carcinoma

Cited by 16 publications

References 41 publications

Inhibition of KPNA4 attenuates prostate cancer metastasis

Inhibition of KPNA4 attenuates prostate cancer metastasis

Integrative molecular network analysis identifies emergent enzalutamide resistance mechanisms in prostate cancer

Ingenuity Pathway Analysis of Gene Expression Profiles in Distal Nerve Stump following Nerve Injury: Insights into Wallerian Degeneration

Contact Info

Product

Resources

About