Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21

Wu, Cheng; Guo, Ergang; Jun, Ming; Sun, Wei; Nie, Xin; Sun, Lu; Peng, Shan; Luo, Min; Liu, Dongbo; Zhang, Linli; Mei, Qi; Long, Guoxian; Hu, Guohong; Hu, Guoqing

doi:10.1016/j.omto.2020.04.007

Cited by 37 publications

(35 citation statements)

References 43 publications

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“…This raises the question of whether EVs can shield the target tumors from DNMT3B inhibitors. Additionally, DNMT3B has been reported to contribute in chemotherapy resistance [ 37 ] and promotes radio-resistance in nasopharyngeal carcinoma [ 38 ]. DNMT3B in BAL EVs mirrors the expression in lung tumor tissue, and this might give a novel opportunity to use it as a marker for chemotherapy and radio-resistance.…”

Section: Discussionmentioning

confidence: 99%

Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?

Carvalho

Moraes

et al. 2020

Cancers

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Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?

Carvalho

Moraes

et al. 2020

Cancers

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“…miR-221-3p and miR-222-3p reduce radiosensitivity in thyroid cancer cells. It was previously reported that EMT was associated with decreased cancer sensitivity to radiation therapy (22)(23)(24)(25). Therefore, a colony formation assay was used to determine the role of miR-221-3p and miR-222-3p in radiosensitivity.…”

Section: Mir-221-3p and Mir-222-3p Regulate The Expression Levels Of P-stat3 Emt-related Markers And Nis In Thyroid Cancer Cellsmentioning

confidence: 99%

miR‑221‑3p and miR‑222‑3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer

Zhong

et al. 2021

Exp Ther Med

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The expression levels of microRNA (miR)-221-3p and miR-222-3p in thyroid cancer have been found to be upregulated compared with those in normal tissues. The present study aimed to determine the effects and potential underlying mechanisms of miR-221-3p and miR-222-3p on the regulation of radioactive iodine ( 131 I) uptake and radiosensitivity of thyroid cancer cells. The potential regulatory target genes of miR-221-3p and miR-222-3p were predicted by bioinformatics analysis, and reverse transcription-quantitative polymerase chain reaction was used to verify miR-221-3p, miR-222-3p and target gene expression levels in thyroid cancer tissues and cell lines. Overexpression of miR-221-3p or miR-222-3p in cell models was performed using lentivirus infection. Knockdown of miR-221-3p and miR-222-3p in cells was achieved using oligonucleotide inhibitor transfection.Western blotting was used to analyze the expression levels of target proteins. In addition, the effects of miR-221-3p and miR-222-3p on the radiosensitivity of thyroid cancer cells were verified using a colony formation assay. The results of the present study revealed that the expression levels of miR-221-3p and miR-222-3p were significantly upregulated, while the expression levels of suppressor of cytokine signaling 3 (SOCS3) were downregulated in thyroid cancer tissues. Furthermore, miR-221-3p and miR-222-3p overexpression downregulated the expression levels of SOCS3, E-cadherin and solute carrier family 5 member 5 (NIS), and upregulated the expression levels of phosphorylated STAT3 and vimentin. Following the overexpression of miR-221-3p or miR-222-3p in the FTC133 and TPC1 cell lines, their radiosensitivity was suppressed. In conclusion, the findings of the present study suggested that miR-221-3p and miR-222-3p may downregulate the expression levels of NIS and promote radioresistance. The potential mechanism was hypothesized to be associated with the miR-221-3p and miR-222-3p targeting of the SOCS3 gene, which may subsequently activate the STAT3 signaling pathway.

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“…The Ras signaling pathway is closely related to the occurrence and progression of most human tumors [ 64 – 67 ]. The activation of RAS-RAF-MEK-MAPK in gene transcription regulation can promote proliferation, migration, and angiogenesis of cancer cells [ 68 – 70 ]. RAS-PI3K interaction is an important signaling node and potential therapeutic target in EGFR-mutant lung cancer [ 71 – 73 ].…”

Section: Discussionmentioning

confidence: 99%

Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression

Zhang

Jiang

et al. 2021

Disease Markers

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Non-small-cell lung cancer (NSCLC) is one of the most devastating diseases worldwide. The study is aimed at identifying reliable prognostic biomarkers and to improve understanding of cancer initiation and progression mechanisms. RNA-Seq data were downloaded from The Cancer Genome Atlas (TCGA) database. Subsequently, comprehensive bioinformatics analysis incorporating gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the protein-protein interaction (PPI) network was conducted to identify differentially expressed genes (DEGs) closely associated with NSCLC. Eight hub genes were screened out using Molecular Complex Detection (MCODE) and cytoHubba. The prognostic and diagnostic values of the hub genes were further confirmed by survival analysis and receiver operating characteristic (ROC) curve analysis. Hub genes were validated by other datasets, such as the Oncomine, Human Protein Atlas, and cBioPortal databases. Ultimately, logistic regression analysis was conducted to evaluate the diagnostic potential of the two identified biomarkers. Screening removed 1,411 DEGs, including 1,362 upregulated and 49 downregulated genes. Pathway enrichment analysis of the DEGs examined the Ras signaling pathway, alcoholism, and other factors. Ultimately, eight prioritized genes (GNGT1, GNG4, NMU, GCG, TAC1, GAST, GCGR1, and NPSR1) were identified as hub genes. High hub gene expression was significantly associated with worse overall survival in patients with NSCLC. The ROC curves showed that these hub genes had diagnostic value. The mRNA expressions of GNGT1 and NMU were low in the Oncomine database. Their protein expressions and genetic alterations were also revealed. Finally, logistic regression analysis indicated that combining the two biomarkers substantially improved the ability to discriminate NSCLC. GNGT1 and NMU identified in the current study may empower further discovery of the molecular mechanisms underlying NSCLC’s initiation and progression.

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Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21

Cited by 37 publications

References 43 publications

Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?

Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?

miR‑221‑3p and miR‑222‑3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer

Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression

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