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Recurrence of mutations in m6A sites. ( A ) Recurrence of mutati...
Published: 23 April 2025
Figure 2.
Recurrence of mutations in m 6 A sites. ( A ) Recurrence of mutations overlapping with m 6 A motifs for mutations classified as 3′UTR, missense, or silent mutations. ( B ) The number of mutations overlapping with m 6 A motifs per gene. ( C ) The number of mutations overlapping with a specific m 6 A
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Effect of m6A motif disruption on gene expression. ( A and B )...
Published: 23 April 2025
Figure 3.
Effect of m 6 A motif disruption on gene expression. ( A and B ) Differential gene expression analysis comparing patients with disrupted (mutated) m 6 A motifs to patients with the same cancer type and intact (wild-type) m 6 A motifs. Significant differentially expressed genes for specific cancer
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Generation of XRCC1 knockout PCa cell lines and their functional v...
Published: 23 April 2025
Figure 2.
Generation of XRCC 1 knockout PCa cell lines and their functional validation. ( A and B ) Immunoblot showing the expression of XRCC1 protein in C4-2B (A) and 22RV1 (B) vector control cells, XRCC1- KO C-1, and XRCC1- KO C-2. Actin was used as a loading control. ( C and D ) Cell growth inhibiti
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XRCC1 depletion enhanced the sensitivity of PCa cells to PARPi. ( ...
Published: 23 April 2025
Figure 3.
XRCC1 depletion enhanced the sensitivity of PCa cells to PARPi. ( A and B ) Cell growth inhibition assay for C4-2B (A) and 22RV1 (B) vector control cells, XRCC1- KO-C1, and XRCC1- KO-C2 with increasing concentrations of PARPi: olaparib (upper), rucaparib (middle), and talazoparib (lower). The c
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XRCC1 knockout increased PARPi-induced chromatin-associated PARP1 ...
Published: 23 April 2025
Figure 5.
XRCC1 knockout increased PARPi-induced chromatin-associated PARP1 in PCa cells. ( A and B ) Immunoblots (left) and quantification (right) show the expression of PARP1 in soluble and chromatin fractions of C4-2B (A) and 22RV1 (B) vector control cells, XRCC1- KO C-1, and XRCC1- KO C-1 + XRCC1 f
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m6A sites and overlap with TCGA mutations. ( A ) Number of disti...
Published: 23 April 2025
Figure 1.
m 6 A sites and overlap with TCGA mutations. ( A ) Number of distinct m 6 A sites in each study and the total number of distinct m 6 A sites in the merged data set (top bar). ( B ) Proportion of m 6 A sites in the canonical DRACH motif. ( C ) Motif discovery in the merged data set. The probability o
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Effect of m6A mutational burden on patient survival. ( A ) Spear...
Published: 23 April 2025
Figure 4.
Effect of m 6 A mutational burden on patient survival. ( A ) Spearman correlation between total mutations and mutations in m 6 A sites. ( B ) M 6 A mutational burden of patients for different cancer types across TCGA. Only patients with more than five total mutations were considered in the analysis.
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Description and effect of gained DRACH motifs. ( A ) Consequences of mutati...
Published: 23 April 2025
Figure 5.
Description and effect of gained DRACH motifs. ( A ) Consequences of mutations on DRACH motifs across all examined mutations. ( B ) Number of gained DRACH motifs per cancer TCGA cancer type. ( C ) Recurrence of 3′UTR, missense, or silent mutations leading to DRACH gains. ( D ) Gene-level analysis of
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XRCC1 knockout increased PARPi-induced DNA damage and damage respo...
Published: 23 April 2025
Figure 4.
XRCC1 knockout increased PARPi-induced DNA damage and damage response signaling in PCa cells. ( A and B ) Representative microscopy images of γ-H2AX foci positive C4-2B (A) and 22RV1 (B) vector control cells, XRCC1- KO C-1, and XRCC1- KO C-1 + XRCC1 following 48 h treatment with PARPi. 0.25 μ
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XRCC1 depletion enhanced PARPi-induced apoptosis. ( A and B ) Re...
Published: 23 April 2025
Figure 7.
XRCC1 depletion enhanced PARPi-induced apoptosis. ( A and B ) Representative apoptosis profiles of C4-2B (A) and 22RV1 (B) vector control cells and XRCC1- KO C-1 following 48 h treatment with 0.5 μM rucaparib using annexin V-PI dual staining-based flow cytometry. ( C and D ) The percent apopto
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XRCC1 expression level dictates the response to PARPi in PCa cells...
Published: 23 April 2025
Figure 8.
XRCC1 expression level dictates the response to PARPi in PCa cells. ( A ) Immunoblot shows the expression of XRCC1 protein in different PCa cell models, including MDA-PCA-2B, C4-2B, LNCaP, PC3, and 22RV1. Ponceau Stain was used as a loading control. ( B ) Cell growth inhibition assay for olaparib (
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Expression level and alteration status of XRCC1 in PCa patients. (...
Published: 23 April 2025
Figure 1.
Expression level and alteration status of XRCC1 in PCa patients. ( A ) Lollipop plot of XRCC1 Log2 median-centered and quantile-scaled normalized gene expression values from TCGA in benign prostate, PCa, and mCRPC patient samples. ( B ) Lollipop of XRCC1 Log2 median-centered and quantile scale
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XRCC1 depletion enhanced PARPi-induced cell cycle arrest. ( A and...
Published: 23 April 2025
Figure 6.
XRCC1 depletion enhanced PARPi-induced cell cycle arrest. ( A and B ) Representative cell cycle profiles of C4-2B (A) and 22RV1 (B) vector control cells and XRCC1- KO C-1 following 48 h treatment with 0.5 μM rucaparib using PI DNA staining-based flow cytometry. ( C and D ) Percent distribution
Journal Article
The role of recurrent somatic mutations that alter conserved m6A motifs in human cancer
NAR Cancer, Volume 7, Issue 2, June 2025, zcaf014, https://doi.org/10.1093/narcan/zcaf014
Published: 23 April 2025
Journal Article
PARP inhibitor response is enhanced in prostate cancer when XRCC1 expression is reduced
NAR Cancer, Volume 7, Issue 2, June 2025, zcaf015, https://doi.org/10.1093/narcan/zcaf015
Published: 23 April 2025
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FLYWCH1 is associated with H3K9me3 and colocalization is lost during resist...
Published: 04 April 2025
Figure 2.
FLYWCH1 is associated with H3K9me3 and colocalization is lost during resistance acquisition. ( A ) Representative single focal plane images of immunofluorescence staining of FLYWCH1 and H3K9me3. Sensitive A2780 and resistant A2780cis cells were fixed and then stained with the indicated antibodies. I
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FLYWCH1 regulates genes associated with resistance development. ( A ) Analy...
Published: 04 April 2025
Figure 4.
FLYWCH1 regulates genes associated with resistance development. ( A ) Analysis of FLYWCH1 expression from RNA-seq data of vehicle and cPt treated A2780 cells with Ctr or FLYWCH1 KD. RNA-seq was performed on cells expressing two independent hairpins (shCtr or shFLY) for 7 weeks and were treated with
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FLYWCH1 KD and early resistance development are associated with changes in ...
Published: 04 April 2025
Figure 6.
FLYWCH1 KD and early resistance development are associated with changes in H3K9me3 at distinct genomic loci. ( A and B ) Heatmaps showing the average H3K9me3 ChIP-seq signal of control and FLYWCH1 KD cells, as well as cells that developed platinum resistance dependent or independent of FLYWCH1 los
