Mesenchymal Stem Cells Cultured in 3D System Inhibit Non-Small Cell Lung Cancer Cells through p38 MAPK and CXCR4/AKT Pathways by IL-24 Regulating

Suo, Feng; Pan, Mengwu; Li, Y.; Yan, Qingying; Hu, Honggang; Hou, Lingling

doi:10.1134/s0026893321030110

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…Ontology revealed that enhancer CpGs from the normal group are weakly associated with pathways commonly linked tumorigenesis (e.g., EMT and renal carcinoma signaling), unlike the tumor enhancer CpGs that were enriched for cancer-associated pathways like MAPK, PTEN, and CXCR4 signaling (Fig. 3 H) [ 32 , 33 ]. Taken together, these findings indicate an overall low level of intra-kidney methylation variability, and that the modest number of CpGs that do display heterogeneity are largely unique to each patient.…”

Section: Resultsmentioning

confidence: 99%

Extensive intratumor regional epigenetic heterogeneity in clear cell renal cell carcinoma targets kidney enhancers and is associated with poor outcome

et al. 2023

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Background Clear cell renal cell cancer (ccRCC), the 8th leading cause of cancer-related death in the US, is challenging to treat due to high level intratumoral heterogeneity (ITH) and the paucity of druggable driver mutations. CcRCC is unusual for its high frequency of epigenetic regulator mutations, such as the SETD2 histone H3 lysine 36 trimethylase (H3K36me3), and low frequency of traditional cancer driver mutations. In this work, we examined epigenetic level ITH and defined its relationships with pathologic features, aspects of tumor biology, and SETD2 mutations. Results A multi-region sampling approach coupled with EPIC DNA methylation arrays was conducted on a cohort of normal kidney and ccRCC. ITH was assessed using DNA methylation (5mC) and CNV-based entropy and Euclidian distances. We found elevated 5mC heterogeneity and entropy in ccRCC relative to normal kidney. Variable CpGs are highly enriched in enhancer regions. Using intra-class correlation coefficient analysis, we identified CpGs that segregate tumor regions according to clinical phenotypes related to tumor aggressiveness. SETD2 wild-type tumors overall possess greater 5mC and copy number ITH than SETD2 mutant tumor regions, suggesting SETD2 loss contributes to a distinct epigenome. Finally, coupling our regional data with TCGA, we identified a 5mC signature that links regions within a primary tumor with metastatic potential. Conclusion Taken together, our results reveal marked levels of epigenetic ITH in ccRCC that are linked to clinically relevant tumor phenotypes and could translate into novel epigenetic biomarkers.

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Section: Resultsmentioning

confidence: 99%