The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma

Chiappetta, Caterina; Puggioni, Chiara; Carletti, Raffaella; Petrozza, Vincenzo; Rocca, Carlo Della; Cristofano, Claudio Di

doi:10.18632/oncotarget.25755

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…A preliminary screen identified 17 nonsynonymous SNVs located on 15 genes, some of which were previously found to be related to osteosarcoma prognosis, such as KMT2C, PALB2, and FGFR4. ( 34‐37 ) Our model demonstrated that polymorphisms on these genes contributed to the different response to chemotherapy, suggesting the potential of gene variants for improving the understanding of tumorigenic mechanisms and predicting disease outcomes. Notably, our results are partly consistent with that the therapeutic response may be influenced by the patients' age; ( 38,39 ) these 17 nonsynonymous SNVs are suggested to be more effective in distinguishing the prognosis of adults.…”

Section: Discussionmentioning

confidence: 86%

FAT1 and MSH2 Are Predictive Prognostic Markers for Chinese Osteosarcoma Patients Following Chemotherapeutic Treatment

Zhou

Sun

Gong

et al. 2020

Journal of Bone and Mineral Research

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Osteosarcoma is characterized by diverse genetic mutations, including single-nucleotide variants (SNVs), which can complicate clinical outcomes of the treatment. This study identified key mutations or polymorphisms in genes that correlate with osteosarcoma prognoses. A total of 110 patients with osteosarcoma were assigned to "good" or "poor" cohorts depending on their 5-year disease-free survival (DFS) after surgery and chemotherapeutic treatment. We performed next-generation sequencing analysis of tumor tissues for prognosis-associated SNVs in 315 tumorigenesis-related genes, followed by modeling of clinical outcomes for these patients using random forest classification via a support vector machine (SVM). Data from the Chinese Millionome Database were used to compare SNV frequency in osteosarcoma patients and healthy people. SVM screening identified 17 nonsynonymous SNVs located in 15 genes, of which rs17224367 and rs3733406 (located in MSH2 and FAT1, respectively) were strongly correlated with osteosarcoma prognosis. These results were verified in a 26-patient validation cohort, confirming that these SNVs could be used to predict prognosis. These results demonstrated that two SNVs located in MSH2 and FAT1 are associated with prognosis of osteosarcoma patients.

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Section: Discussionmentioning

confidence: 86%

FAT1 and MSH2 Are Predictive Prognostic Markers for Chinese Osteosarcoma Patients Following Chemotherapeutic Treatment

Zhou

Sun

Gong

et al. 2020

Journal of Bone and Mineral Research

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“…Further, the gene KMT2C , which is mutated in 67% of all OS samples, involved in OS carcinogenesis and progression [ 61 ]. Similar to results of our study, the exome analysis shows a high load of somatic variations in KMT2C , which can have histone modification-related activity in OS [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways

Southekal

Shakyawar

Bajpai

et al. 2023

Cancers

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Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. Results revealed the enrichment of molecular pathways including Wnt signaling, Calcium signaling, and PI3K-Akt signaling in the OS tumors. Survival analyses showed that the expression levels of several genes such as RAMP1, CRIP1, CORT, CHST13, and DDX60L, miRNAs and lncRNAs were associated with survival of OS patients. Molecular subtyping using Cluster-Of-Clusters Analysis (COCA) for mRNA, lncRNA, and miRNA expression; DNA methylation; and mutation data from the TARGET dataset revealed two distinct molecular subtypes, each with a distinctive gene expression profile. Between the two subtypes, three upregulated genes, POP4, HEY1, CERKL, and seven downregulated genes, CEACAM1, ABLIM1, LTBP2, ISLR, LRRC32, PTPRF, and GPX3, associated with OS metastasis were found to be differentially regulated. Thus, the molecular subtyping results provide a strong basis for classification of OS patients that could be used to develop better prognostic treatment strategies.

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“…Studies have found that miR-93-5p is closely related to tumorigenesis [ 18 ]. The KMT2C gene has mutations or deletions in many tumors, including leukemia, liver cancer, pancreatic cancer, gastric cancer, cholangiocarcinoma, ovarian cancer, and bladder transitional cell carcinoma [ 19 , 20 ]. In recent years, several studies have found that lncRNAs may play a biological role by regulating downstream target genes through miRNA adsorption processes [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

XIST lost induces ovarian cancer stem cells to acquire taxol resistance via a KMT2C-dependent way

2020

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Background/aims: The expression levels of long non-coding RNA XIST are significantly associated with paclitaxel (Pac) sensitivity in ovarian cancer, but the mechanism of action remains unclear. Therefore, this experimental design was based on lncRNA XIST analysis to regulate the effect of XIST on the tumor stem cell and paclitaxel sensitivity in ovarian cancer. Methods: Sphere assay and fluorescence activated cell sorting (FACS) were used to determine the expression levels of XIST and sensitivity to paclitaxel treatment. The effect of the proliferation was detected by MTT assay. Target gene prediction and screening, luciferase reporter assays were used to validate downstream target genes for lncRNA XIS and KMT2C. The expression of KMT2C was detected by RT-qPCR and Western blotting. RT-qPCR was used to detect the expression of cancer stem cell-associated genes SOX2, OCT4 and Nanog. The tumor changes in mice were detected by in vivo experiments in nude mice. Results: There was an inverse correlation between the expression of XIST and cancer stem cell (CD44 + /CD24−) population. XIST promoted methylation of histone H3 methylation at lysine 4 by enhancing the stability of lysine (K)-specific methyltransferase 2C (KMT2C) mRNA. XIST acted on the stability of KMT2C mRNA by directly targeting miR-93-5p. Overexpression of miR-93-5p can reverse the XIST overexpression-induced KMT2C decrease and sphere number increase. Overexpression of KMT2C inhibited XIST silencing-induced proliferation of cancer stem cells, and KMT2C was able to mediate paclitaxel resistance induced by XIST in ovarian cancer. The study found that XIST can affect the expression of KMT2C in the ovarian cancer via targeting miR-93-5p. Conclusion: XIST promoted the sensitivity of ovarian cancer stem cells to paclitaxel in a KMT2C-dependent manner.

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The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma

Cited by 5 publications

References 38 publications

FAT1 and MSH2 Are Predictive Prognostic Markers for Chinese Osteosarcoma Patients Following Chemotherapeutic Treatment

FAT1 and MSH2 Are Predictive Prognostic Markers for Chinese Osteosarcoma Patients Following Chemotherapeutic Treatment

Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways

XIST lost induces ovarian cancer stem cells to acquire taxol resistance via a KMT2C-dependent way

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