Integrated Oncogenomic Profiling of Copy Numbers and Gene Expression in Lung Adenocarcinomas without <i>EGFR</i> Mutations or <i>ALK</i> Fusion

Luo, Yanzhuo; Li, Bingjin; Zhang, Guangxin; He, Yuxiao; Bae, Jeeyoo Hope; Hu, Fengping; Cui, Ranji; Liu, Runhua; Wang, Zhou; Wang, Lizhong

doi:10.7150/jca.23909

Cited by 6 publications

(5 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are reported associations between PTPRD variation and a number of cancers or their responses to treatment . While the details of these associations are beyond the scope of this paper, we note that most come from genotyping tumors or tumor‐derived cell lines and that none of these associations focuses on the mid‐gene regions that we have associated with a number of brain phenotypes and levels of PTPRD expression.…”

Section: Ptprd Variation and Brain Phenotypes: Current Supportmentioning

confidence: 93%

PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes

Uhl

Martínez

2019

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Receptor‐type protein tyrosine phosphatase, receptor type D (PTPRD) has likely roles as a neuronal cell adhesion molecule and synaptic specifier. Interest in its neurobiology and genomics has been stimulated by results from human genetics and mouse models for phenotypes related to addiction, restless leg syndrome, neurofibrillary pathology in Alzheimer's disease, cognitive impairment/intellectual disability, mood lability, and obsessive‐compulsive disorder. We review PTPRD's discovery, gene family, candidate homomeric and heteromeric binding partners, phosphatase activities, brain distribution, human genetic associations with nervous system phenotypes, and mouse model data relevant to these phenotypes. We discuss the recently reported discovery of the first small molecule inhibitor of PTPRD phosphatase, the identification of its addiction‐related effects, and the implications of these findings for the PTPRD‐associated brain phenotypes. In assembling PTPRD neurobiology, human genetics, and mouse genetic and pharmacological datasets, we provide a compelling picture of the roles played by PTPRD, its variation, and its potential as a target for novel therapeutics.

show abstract

Section: Ptprd Variation and Brain Phenotypes: Current Supportmentioning

confidence: 93%

PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes

Uhl

Martínez

2019

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…Quantitative analysis of copy numbers was conducted by QIAGEN qBiomarker Copy Number PCR assays (QIAGEN, Germantown, MD, USA) based on a 7500 Real Time PCR System (Thermo Fisher Scientific) as previously described 58, 59 . All qBiomarker Copy Number PCR Assays were designed for unique regions of the genome.…”

Section: Methodsmentioning

confidence: 99%

“…The reference assay recognizes a stable sequence that appears in the human genome more than 40 times and whose copy number is not affected or minimally affected by local genomic changes. Relative gene copy numbers for each specimen were calculated as 2 × (tumor copy number/MRef copy number) as described previously 59 .…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer

Wang

Liu

et al. 2019

Oncogene

Self Cite

View full text Add to dashboard Cite

The chromosome 8q24.21 locus, which contains the proto-oncogene c- MYC , long non-coding RNA PVT1, and microRNAs (miRs), is the most commonly amplified region in human prostate cancer. A long-range interaction of genetic variants with c- MYC or long non-coding PVT1 at this locus contributes to the genetic risk of prostate cancer. At this locus is a cluster of genes for six miRs (miR-1204, −1205, −1206, −1207–3p, −1207–5p, and −1208), but their functional role remains elusive. Here, the copy numbers and expressions of miRs-1204~1208 were investigated using quantitative PCR for prostate cancer cell lines and primary tumors. The data revealed that copy numbers and expression of miR-1205 were increased in both castration-resistant prostate cancer cell lines and in primary tumors. In castration-resistant prostate cancer specimens, the copy number at the miR-1205 locus correlated with expression of miR-1205. Furthermore, functional analysis with an miR-1205 mimic, an miR-1205 inhibitor, and CRISPR/Cas9 knockout revealed that, in human prostate cancer cells, miR-1205 promoted cell proliferation and cell cycle progression and inhibited hydrogen peroxide-induced apoptosis. In these cells, miR-1205 downregulated expression of the Egl-9 family hypoxia inducible factor 3 ( EGLN3 ) gene and targeted a site in its 3’-untranslated region to downregulate its transcriptional activity. Thus, by targeting EGLN3, miR-1205 has an oncogenic role and may contribute to the genetic risk of castration-resistant prostate cancer.

show abstract

“…Quantitative analysis of copy numbers was conducted by QIAGEN qBiomarker Copy Number PCR assays (Qiagen) as described previously (21).…”

Section: Quantification Of Gene Copy Numbersmentioning

confidence: 99%

Loss of FOXP3 and TSC1 Accelerates Prostate Cancer Progression through Synergistic Transcriptional and Posttranslational Regulation of c-MYC

Wei

et al. 2019

Cancer Research

Self Cite

View full text Add to dashboard Cite

Although c-MYC and mTOR are frequently activated proteins in prostate cancer, any interaction between the two is largely untested. Here, we characterize the functional cross-talk between FOXP3-c-MYC and TSC1-mTOR signaling during tumor progression. Deletion of Tsc1 in mouse embryonic fibroblasts (MEF) decreased phosphorylation of c-MYC at threonine 58 (pT58) and increased phosphorylation at serine 62 (pS62), an observation validated in prostate cancer cells. Conversely, inhibition of mTOR increased pT58 but decreased pS62. Loss of both FOXP3 and TSC1 in prostate cancer cells synergistically enhanced c-MYC expression via regulation of c-Myc transcription and protein phosphorylation. This crosstalk between FOXP3 and TSC1 appeared to be mediated by both the mTOR-4EBP1-c-MYC and FOXP3-c-MYC pathways. In mice, Tsc1 and Foxp3 double deletions in the prostate led to prostate carcinomas at an early age; this did not occur in these mice with an added c-Myc deletion. In addition, we observed synergistic antitumor effects of cotreating mice with inhibitors of mTOR and c-MYC in prostate cancer cells and in Foxp3 and Tsc1 double-mutant mice. In human prostate cancer, loss of nuclear FOXP3 is often accompanied by low expression of TSC1. Because loss of FOXP3 transcriptionally induces c-Myc expression and loss of TSC1 activates mTOR signaling, these data suggest cross-talk between FOXP3-c-MYC and TSC1-mTOR signaling that converges on c-MYC to regulate tumor progression. Coadministration of c-MYC and mTOR inhibitors may overcome the resistance to mTOR inhibition commonly observed in prostate cancer cells. Significance: These results establish the principle of a synergistic action of TSC1 and FOXP3 during prostate cancer progression and provide new therapeutic targets for patients who have prostate cancer with two signaling defects.

show abstract

Integrated Oncogenomic Profiling of Copy Numbers and Gene Expression in Lung Adenocarcinomas without EGFR Mutations or ALK Fusion

Cited by 6 publications

References 51 publications

PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes

PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes

MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer

Loss of FOXP3 and TSC1 Accelerates Prostate Cancer Progression through Synergistic Transcriptional and Posttranslational Regulation of c-MYC

Contact Info

Product

Resources

About