DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining

Chen, Jianlin; Ding, Junping; Huang, Wenjie; Sun, Lin; Chen, Jinping; Liu, Yangyang; Zhan, Qianmei; Gao, Gan; He, Xiaoling; Qiu, Guowen; Long, Peiying; Wei, Lishu; Lu, Zhen-Ni; Sun, Yifan

doi:10.3389/fgene.2021.699242

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…Moreover, CDK1 and MAD2L1 were reported by Lu et al as prognostic markers in rhabdomyosarcoma [ 38 ]. To the best of our knowledge, this is the first comprehensive study to assess the expression of MAD2L1 in HCC using TCGA database [ 39 ]. We provided compelling evidence that MAD2L1 gene expression levels are significantly higher in HCC patients than in adjacent paraneoplastic tissues, as confirmed by IHC.…”

Section: Discussionmentioning

confidence: 99%

Identification of MAD2L1 as a Potential Biomarker in Hepatocellular Carcinoma via Comprehensive Bioinformatics Analysis

Chen

Yang

Zhang

et al. 2022

BioMed Research International

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Background. Hepatocellular carcinoma (HCC) is widely acknowledged as a malignant tumor with rapid progression, high recurrence rate, and poor prognosis. At present, there is a paucity of reliable biomarkers at the clinical level to guide the management of HCC and improve patient outcomes. Our research is aimed at assessing the prognostic value of MAD2L1 in HCC. Methods. Four datasets, GSE121248, GSE101685, GSE85598, and GSE62232, were selected from the GEO database to analyze differentially expressed genes (DEGs) between HCC and normal liver tissues. After functional analysis, we constructed a protein-protein interaction network (PPI) for DEGs and identified core genes in this network with high connectivity with other genes. We assessed the relationship between core genes and the pathogenesis and prognosis of HCC. Finally, we explored the gene regulatory signaling mechanisms involved in HCC pathogenesis. Results. 145 DEGs were screened from the intersection of the four GEO datasets. MAD2L1 was associated with most genes according to the PPI network and was selected as a candidate gene for further study. Survival analysis suggested that high MAD2L1 expression in HCC correlated with a worse prognosis. In addition, real-time quantitative PCR (RT-qPCR), western blot (WB), and immunohistochemistry (IHC) findings suggested that the expression of MAD2L1 was abnormally increased in HCC tissues and cells compared to paraneoplastic tissues and normal hepatocytes. Conclusion. We found that high MAD2L1 expression in HCC was significantly associated with overall patient survival and clinical features. We also explored the potential biological properties of this gene.

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Section: Discussionmentioning

confidence: 99%

Identification of MAD2L1 as a Potential Biomarker in Hepatocellular Carcinoma via Comprehensive Bioinformatics Analysis

Chen

Yang

Zhang

et al. 2022

BioMed Research International

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“…DNASE1L3 is correlated with breast cancer signalling, renal clear cell carcinoma staging 10,11 . Furthermore, DNASE1L3 was found to be a potential prognostic biomarker in lung adenocarcinoma and colon cancer 12,13 . Recent studies reported that DNASE1L3 could inhibit glycolysis in hepatoma cells and promote the tricarboxylic acid cycle involved in PTPN2‐HK2 and CEBPβ‐p53‐PFK1 pathways, thereby inhibiting HCC progression 14,15 .…”

Section: Introductionmentioning

confidence: 99%

“…10,11 Furthermore, DNASE1L3 was found to be a potential prognostic biomarker in lung adenocarcinoma and colon cancer. 12,13 Recent studies reported that DNASE1L3 could inhibit glycolysis in hepatoma cells and promote the tricarboxylic acid cycle involved in PTPN2-HK2 and CEBPβ-p53-PFK1 pathways, thereby inhibiting HCC progression. 14,15 Based on various bioinformatic analyses, we found that the role of DNASE1L3 is associated with HCC proliferation, invasion and metastasis, but the underlying molecular mechanisms is unclear.…”

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confidence: 99%

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

Yan

et al. 2022

Cell Proliferation

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As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β‐catenin destruction complex (GSK‐3β and Axin), promotes the ubiquitination degradation of β‐catenin, and inhibits its nuclear transfer, thus, decreasing c‐Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

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“…A previous study reported that DNASE1L3 is downregulated in LUAD (12). An additional study found that mRNA and protein expression levels of DNASE1L3 in patients with LUAD are significantly lower than those in normal tissue and low expression of DNASE1L3 is significantly correlated with higher pathological stage, T stage and poor prognosis, making it an independent factor for predicting the overall survival rate (13). The specific role of DNASE1L3 in LUAD, to the best of our knowledge, has not yet been reported.…”

Section: Introductionmentioning

confidence: 85%

DNASE1L3 regulation by transcription factor FOXP2 affects the proliferation, migration, invasion and tube formation of lung adenocarcinoma

2022

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Lung adenocarcinoma (LUAD) is prone to bone metastasis, resulting in poor prognosis. The present study aimed to detect the expression of deoxyribonuclease 1-like 3 (DNASE1L3) and forkhead-box P2 (FOXP2) in LUAD cells to investigate the role of DNASE1L3 in the regulation of proliferation, migration, invasion and tube formation of LUAD cells and how FOXP2 affects DNASE1L3 expression. The expression of DNASE1L3 and FOXP2 in LUAD cells was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The transfection efficiency of DNASE1L3 overexpression plasmids, FOXP2 overexpression or interference plasmids into A549 cells was also confirmed by RT-qPCR and western blotting. The viability, proliferation, migration and invasion and tube formation of LUAD cells following transfection was in turn detected by MTT, EdU staining, wound healing, Transwell and tube formation assay. The expression of proteins associated with epithelial-mesenchymal transformation and tube formation was detected by western blotting. Binding between DNASE1L3 and FOXP2 was confirmed by dual-luciferase reporter assay and chromatin immunoprecipitation. Gene Expression Profiling Interactive Analysis database predicted that underexpression of DNASE1L3 in LUAD was associated with poor prognosis. DNASE1L3 expression was decreased in LUAD cells and overexpression of DNASE1L3 inhibited the proliferation, migration, invasion and tube formation of LUAD cells. Transcription factor FOXP2 positively regulated DNASE1L3 transcription in LUAD cells. FOXP2 was also underexpressed in LUAD cells and downregulation of FOXP2 promoted proliferation, migration, invasion and tube formation of LUAD cells, which was reversed by overexpression of DNASE1L3. In conclusion, DNASE1L3 was positively regulated by transcription factor FOXP2 and overexpression inhibited proliferation, migration, invasion and tube formation of LUAD cells.

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DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining

Cited by 7 publications

References 38 publications

Identification of MAD2L1 as a Potential Biomarker in Hepatocellular Carcinoma via Comprehensive Bioinformatics Analysis

Identification of MAD2L1 as a Potential Biomarker in Hepatocellular Carcinoma via Comprehensive Bioinformatics Analysis

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

DNASE1L3 regulation by transcription factor FOXP2 affects the proliferation, migration, invasion and tube formation of lung adenocarcinoma

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