KMT2D promotes proliferation of gastric cancer cells: evidence from ctDNA sequencing

Li, Qiaolian; Wu, Riping; Wu, Fan; Chen, Qiang

doi:10.1002/jcla.23721

Cited by 12 publications

(9 citation statements)

References 29 publications

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“…KMT2D methylates lysine 4 in histone H3 in several cancers. [29][30][31] Our findings suggest that hsa_circ_0000977 may also promote the progression of esophageal cancer through the hsa_circ_0000977/miR-874-3p/KMT2D axis. However, there is a lack of reports on OSTIM in tumor-related mechanisms.…”

Section: And Kmt2dmentioning

confidence: 75%

Upregulation of hsa_circ_0000977 participates in esophageal squamous cancer progression by sponging miR‐874‐3p

et al. 2022

Clinical Laboratory Analysis

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Background Esophageal squamous cell carcinoma (ESCC) is one of the most common clinical malignancies of the digestive system, characterized by high mortality but not evident early symptoms. Molecular markers for diagnostic and outcome prediction are urgently needed. Circular RNAs might play essential roles in the progression of ESCC. Methods Hsa_circ_0000977 was identified using circRNA microarrays and qRT‐PCR. The diagnostic value of hsa_circ_0000977 was calculated. We also examined in vitro cell functions in ECA109 and TE12 ESCC cells to determine the effect of hsa_circ_0000977. A dual‐luciferase reporter vector validated the binding of hsa_circ_0000977 to miR‐874‐3p. Results The top 10 significantly upregulated circRNAs from microarray assays were hsa_circ_0000977, hsa_circ_0006220, hsa_circ_0043278, hsa_circ_0000691, hsa_circ_0000288, hsa_circ_0000367, hsa_circ_0021647, hsa_circ_0006440, hsa_circRNA_405571 and hsa_circRNA_100790, while the top 10 significantly downregulated circRNAs were hsa_circ_0008389, hsa_circ_0089763, hsa_circ_0089762, hsa_circ_0000102, hsa_circ_0001714, hsa_circ_0089761, hsa_circ_0007326, hsa_circ_0001549, hsa_circ_0005133 and hsa_circRNA_405965. Hsa_circ_0000977 was significantly upregulated in ESCC ( p < 0.01) and had diagnostic value in ESCC. The hsa_circ_0000977 expression level was related to the pT stage and numbers of lymph nodes in ESCC patients. Elevated hsa_circ_0000977 promoted cell proliferation, migration and inhibited apoptosis in ESCC cells. Hsa_circ_0000977 might function as a micro‐RNA sponge to competitively bind miR‐874‐3p. Conclusion Disordered hsa_circ_0000977 expression can promote carcinogenesis in ESCC and might serve as a diagnostic biomarker to evaluate the occurrence and development of esophageal cancer.

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Section: And Kmt2dmentioning

confidence: 75%

Upregulation of hsa_circ_0000977 participates in esophageal squamous cancer progression by sponging miR‐874‐3p

et al. 2022

Clinical Laboratory Analysis

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“…When comparing the two groups, we found that the frequencies of mutations in KMT2B , SOX1 , and FGF12 were significantly higher in HBV-positive group than in HBV-negative group ( P = 0.035, Figure S3 and Figure 3B ), and the frequencies of mutations in KMT2D and TUBB2B showed an increasing mutated tendency in HBV-positive group than in the HBV-negative ( P = 0.315, Figure S3 and Figure 3B ), suggesting that these mutated genes may exert a biological impact on HBV-infected patients with GC. Recently, several studies had revealed that KMT2D ( Li et al., 2021 ; Numakura and Uozaki, 2021 ) and SOX1 ( Yin et al., 2020 ) were implicated in the initiation and progression of GC, whereas the other three frequently mutated genes have not been investigated. Thus, the mRNA expression levels of three frequently mutated genes in GC were analyzed by using TCGA datasets.…”

Section: Resultsmentioning

confidence: 99%

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer

Luo

et al. 2022

Front. Cell. Infect. Microbiol.

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Hepatitis B virus (HBV) infection has been reported to be associated with gastric cancer (GC). Nonetheless, no study has revealed the role of HBV infection in the survival of patients with GC, and the mutation profiles of HBV-infected patients with GC have never been documented. Here, we performed an updated meta-analysis and found a significantly increased risk of GC in HBV-infected individuals (sOR, 1.29; 95% CI, 1.22-1.37). Furthermore, we observed that in the Anhui area, the rate of serum HBsAg positivity (OR, 1.62; 95% CI, 1.03-2.55) was significantly higher in GC patients than in controls. Moreover, our results showed that HBV-positive patients had significantly worse disease-free survival (HR, 1.98; 95% CI, 1.39-2.82) and overall survival (HR, 1.84; 95% CI, 1.19-2.85) than HBV-negative patients. The results of Cox proportional hazards regression proved that HBV infection was an independent adverse prognostic factor in GC. Furthermore, by performing targeted-NGS, we found unique mutation profiles in HBV-infected GC samples, including five frequently mutated protein-coding genes (KMT2B, KMT2D, SOX1, FGF12, and TUBB2B). Expression and survival analyses of these genes identified three novel candidate genes that may have potential roles in GC development. Gene Ontology enrichment analysis showed that the recurrent mutations in HBV-positive GC samples were related to cell proliferation, cell migration, and transcription. Taking together, our study proved that HBV infection is an independent prognostic factor in GC patients. The unique mutation profiles of HBV-infected patients with GC open a new research direction toward the underling mechanism between HBV infection and GC.

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“…In addition, the high frequent mutations of KMT2D in high latitudes and the poor outcome in high latitudes were consistent with their results. Multiple studies have shown that mutations in these genes could influence the overall survival of GC patients ( Choi et al, 2015 ; Chen et al, 2019 ; Li et al, 2021 ; Yu et al, 2021 ). All these results suggest that the different mutational ratios of the same genes and the mutations in specific mutational genes might all be the causes of the difference between the two sample groups.…”

Section: Resultsmentioning

confidence: 99%

Multidimensional difference analysis in gastric cancer patients between high and low latitude

et al. 2022

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Genetic variation has been shown to affect tumor growth and progression, and the temperature at different latitudes may promote the evolution of genetic variation. Geographical data with latitudinal information is of importance to understand the interplay between genetic variants and environmental influence, such as the temperature, in gastric cancer (GC). In this study, we classified the GC samples from The Cancer Genome Atlas database into two groups based on the latitudinal information of patients and found that GC samples with low-latitude had better clinical outcomes. Further analyses revealed significant differences in other clinical factors such as disease stage and grade between high and low latitudes GC samples. Then, we analyzed the genomic and transcriptomic differences between the two groups. Furthermore, we evaluated the activity score of metabolic pathways and infiltrating immune cells in GC samples with different latitudes using the single-sample gene set enrichment analysis algorithm. These results showed that GC samples at low-latitude had lower tumor mutation burden and subclones as well as higher DNA repair activities. Meanwhile, we found that most immune cells were associated with the prognosis of low-latitude GC patients. At last, we constructed and validated an immune-related prognostic model to evaluate the prognosis of GC samples at different latitudes. This study has provided a further understanding of the geographical contribution to GC at the multiomic level and may benefit the individualized treatment of GC patients at different latitudes.

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KMT2D promotes proliferation of gastric cancer cells: evidence from ctDNA sequencing

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 12 publications

References 29 publications

Upregulation of hsa_circ_0000977 participates in esophageal squamous cancer progression by sponging miR‐874‐3p

Upregulation of hsa_circ_0000977 participates in esophageal squamous cancer progression by sponging miR‐874‐3p

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer

Multidimensional difference analysis in gastric cancer patients between high and low latitude

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