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

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.

Integrative analysis of deoxyribonuclease 1-like 3 as a potential biomarker in renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma (RCC), is insensitive to radiotherapy and chemotherapy after surgery. Deoxyribonuclease 1-like 3 (DNASE1L3), an endonuclease that cleaves both membrane-encapsulated single- and double-stranded DNA, suppresses cell cycle progression, proliferation and metabolism in hepatocellular carcinoma cells. There is currently no established link between DNASE1L3 and RCC inhibition. We are gonging to explored the mechanism underlying the relationship between DNASEL1L3 and RCC. Methods: RNA sequencing data for RCC tissue and peritumoral tissue were downloaded from The Cancer Genome Atlas database and analyzed. The expression levels of DNASE1L3 in RCC and normal samples were verified using the Gene Expression Omnibus (GEO) database, Human Protein Atlas database and western blotting. The role and potential mechanism of DNASE1L3 were investigated by analysis of immune-related databases and wound healing, invasion, cell counting kit 8 and immunofluorescence assays. Results: We revealed that DNASE1L3 expression was downregulated in RCC group compared with control group [The Cancer Genome Atlas (TCGA): 7.98 vs. 10.87, P<0.001]. Meanwhile, DNASE1L3 expression correlated with the clinical characteristics of patients. Patients with low DNASE1L3 expression had worse survival (P<0.001) and larger (r=-0.32, P<0.001) and heavier tumors (r=-0.17, P<0.001). DNASE1L3 overexpression inhibited the proliferation (786-O: 0.135±0.014 vs. 0.322±0.027, P<0.001) and invasion (786-O: 1,479±134 vs. 832±67, P<0.05) of RCC cells. The expression of DNASE1L3 was significantly correlated with the tumor immune microenvironment and drug sensitivity in ccRCC. Moreover, the level of the key phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway protein P-AKT was decreased in the group of cells transfected with DNASE1L3. Conclusions: This study strongly suggest that DNASE1L3 may be a promising potential biomarker for the diagnosis and treatment of ccRCC patients.

Deoxyribonuclease 1-like 3 may be a potential prognostic biomarker associated with immune infiltration in colon cancer.

Colon adenocarcinoma (COAD) is a common cancer of the digestive system. It's high morbidity and mortality make it one of the leading causes of cancer deaths. In this study, we studied the microenvironment of colon cancer to find new diagnostic markers and immunotherapy targets for colon cancer. Tumor purity of colon cancer samples in TCGA database were obtained by ESTIMATE algorithm. Then, we analyzed the association of Immune, Stromal, and Estimate scores with tumor prognosis and clinicopathological features. By comparing the gene expression profiles between tumor and normal samples, the high and low immune score groups, 117 intersecting differentially expressed genes (DEGs) were obtained. The function, molecular pathway, and prognostic value of these 117 DEGs pointed toward the importance of deoxyribonuclease 1-like 3 (DNASE1L3). Validation results from multiple databases showed low expression of DNASE1L3 in colon cancer. A single GSEA and correlation analysis of immune cells indicated that DNASE1L3 was closely related to immunity. The low expression of DNASE1L3 in colon cancer samples was measured with qRT-PCR. The scratch and cell proliferation experiments suggested that DNASE1L3 may affect cell migration. Therefore, we concluded that DNASE1L3 might be a biomarker associated with prognosis and immune infiltration in colon cancer.

Serum Deoxyribonuclease 1-like 3 is a potential biomarker for diagnosis of ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease with high disability rate, and it is sometimes difficult to distinguish from generalized osteoarthritis (GOA). Deoxyribonuclease 1-like 3 (DNASE1L3) was associated with a variety of autoimmune diseases. However, the serum DNASE1L3 level in AS and GOA remain unreported. Herein, this study was designed to gauge serum DNASE1L3 level in patients with AS and GOA, and to discern the utility of serum DNASE1L3 as a biomarker for assessing the severity of patients with AS. METHODS: The study population consisted of 60 patients with AS, 60 patients with GOA and 60 control subjects. Serum DNASE1L3 levels were measured using enzyme-linked immunosorbent assay (ELISA) assay. Disease activity were assessed with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. RESULTS: Our data showed that serum DNASE1L3 levels were significantly higher in patients with AS than that of the healthy controls and patients with GOA. Serum DNASE1L3 levels in patients with AS were positively correlated with BASDAI scores, C3 and C-reactive protein (CRP). Furthermore, serum DNASE1L3 showed higher discriminatory accuracy in the diagnosis of AS from GOA (AUC = 0.851, sensitivity = 78.33% and specificity = 81.67%). CONCLUSIONS: Elevated Serum DNASE1L3 levels in patients with AS were significantly associated with the clinic features and disease activity. DNASE1L3 could be a serum biomarker with a positive diagnostic value in patients with AS, and which could be used as a differential diagnostic indicator for GOA and AS.