DataSheet_1_Detection of somatic copy number deletion of the CDKN2A gene by quantitative multiplex PCR for clinical practice.zip

BackgroundA feasible method to detect somatic copy number deletion (SCND) of genes is still absent to date.MethodsInterstitial base-resolution deletion/fusion coordinates for CDKN2A were extracted from published articles and our whole genome sequencing (WGS) datasets. The copy number of the CDKN2A gene was measured with a quantitative multiplex PCR assay P16-Light and confirmed with whole genome sequencing (WGS).ResultsEstimated common deletion regions (CDRs) were observed in many tumor suppressor genes, such as ATM, CDKN2A, FAT1, miR31HG, PTEN, and RB1, in the SNP array-based COSMIC datasets. A 5.1 kb base-resolution CDR could be identified in >90% of cancer samples with CDKN2A deletion by sequencing. The CDKN2A CDR covers exon-2, which is essential for P16INK4A and P14ARF synthesis. Using the true CDKN2A CDR as a PCR target, a quantitative multiplex PCR assay P16-Light was programmed to detect CDKN2A gene copy number. P16-Light was further confirmed with WGS as the gold standard among cancer tissue samples from 139 patients.ConclusionThe 5.1 kb CDKN2A CDR was found in >90% of cancers containing CDKN2A deletion. The CDKN2A CDR was used as a potential target for developing the P16-Light assay to detect CDKN2A SCND and amplification for routine clinical practices.</p

DataSheet_2_Detection of somatic copy number deletion of the CDKN2A gene by quantitative multiplex PCR for clinical practice.pdf

BackgroundA feasible method to detect somatic copy number deletion (SCND) of genes is still absent to date.MethodsInterstitial base-resolution deletion/fusion coordinates for CDKN2A were extracted from published articles and our whole genome sequencing (WGS) datasets. The copy number of the CDKN2A gene was measured with a quantitative multiplex PCR assay P16-Light and confirmed with whole genome sequencing (WGS).ResultsEstimated common deletion regions (CDRs) were observed in many tumor suppressor genes, such as ATM, CDKN2A, FAT1, miR31HG, PTEN, and RB1, in the SNP array-based COSMIC datasets. A 5.1 kb base-resolution CDR could be identified in >90% of cancer samples with CDKN2A deletion by sequencing. The CDKN2A CDR covers exon-2, which is essential for P16INK4A and P14ARF synthesis. Using the true CDKN2A CDR as a PCR target, a quantitative multiplex PCR assay P16-Light was programmed to detect CDKN2A gene copy number. P16-Light was further confirmed with WGS as the gold standard among cancer tissue samples from 139 patients.ConclusionThe 5.1 kb CDKN2A CDR was found in >90% of cancers containing CDKN2A deletion. The CDKN2A CDR was used as a potential target for developing the P16-Light assay to detect CDKN2A SCND and amplification for routine clinical practices.</p

Gd–Metallofullerenol Nanomaterial Suppresses Pancreatic Cancer Metastasis by Inhibiting the Interaction of Histone Deacetylase 1 and Metastasis-Associated Protein 1

The treatment of pancreatic cancer frequently fails due to local recurrence and hepatic metastasis. Our previous study found that Gd@C₈₂(OH)₂₂ can suppress pancreatic cancer by inhibiting MMP-2/9 expression. In this study, we further explored the epigenetic mechanism of Gd@C₈₂(OH)₂₂ in human pancreatic cancer metastasis. Gd@C₈₂(OH)₂₂ suppressed tumor metastasis through down-regulation of metastasis-associated protein 1 (MTA1), HDAC1, HIF-1α, and MMP-2/9 and up-regulation of reversion-cysteine protein with the <i>Kazal</i> motif (RECK). The level of acetylation was increased in the promoter region of the RECK gene after Gd@C₈₂(OH)₂₂ treatment. The interaction of MTA1, HDAC1, and HIF-1α was inhibited by Gd@C₈₂(OH)₂₂. Furthermore, large-scale molecular dynamics simulations revealed Gd@C₈₂(OH)₂₂ could serve as an effective HDAC inhibitor to the protein–protein association between HDAC1 and MTA1, especially through MTA1’s SANT and ELM2 dimerization domains. Our findings implicate Gd@C₈₂(OH)₂₂ as a novel HDAC inhibitor acting to increase RECK expression by suppressing the MTA1/HDAC1 co-repressor complex. Gd@C₈₂(OH)₂₂ may serve as a potential HDAC1 inhibitor to suppress pancreatic cancer cell invasion and metastasis both <i>in vitro</i> and <i>in vivo</i>. According to computer analysis and experimental validation, Gd@C₈₂(OH)₂₂ activates RECK expression by inhibiting the interaction of HDAC1 and MTA1

Additional file 1: Figure S1. of Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein induce cell differentiation in gastric cancer

A model illustrating the molecular functions of MAWBP and MAWD in GC. The presence of MAWBP enhances the inhibitory effect of MAWD on the TGF-beta signaling pathway. The MAWD-MAWBP complex inhibits the phosphorylation and nuclear translocation of Smads, which influences the expression of downstream genes, as shown by, for example, the downregulated expression of the transcription factor Snail. Snail does not efficiently bind to the E-box upstream of the E-cadherin gene, and thus the expression of E-cadherin is increased. This pathway influences the differentiation of GC cells. (TIFF 945 kb