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Chondroitin sulfate synthase 3 (CHSY3) is an important enzyme that regulates glycosylation, but its role in tumors has not been determined. Here, we showed that high CHSY3 expression promotes proliferation in gastric cancer (GC) cells and is associated with poor prognosis in GC patients. We analyzed the immunohistochemistry data of 150 gastric cancer patients to determine the clinicopathological and survival significance of CHSY3. Immunofluorescence was used to detect the colocalization of CHSY3 with infiltrating immune cells. Additionally, CHSY3 was predominantly found in tumor tissues and showed higher abundance compared to matched adjacent tissues. High CHSY3 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis revealed that CHSY3 expression was significantly positively correlated with tumor-associated macrophage (TAM) infiltration. Moreover, after knocking down CHSY3, the proliferation of cells was decreased, and the migration ability was reduced, as shown by scratch, monoclonal and transwell assays. In conclusion, this study revealed that CHSY3 has a tumor-promoting effect on GC, suggesting a novel therapeutic strategy against this disease. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) has been identified as one of the predominant factors leading to persistent low back pain and disability in middle-aged and elderly people. Dysregulation of Prostaglandin E2 (PGE2) can cause IDD, while low-dose celecoxib can maintain PGE2 at the physiological level and activate the skeletal interoception. Here, as nano fibers have been extensively used in the treatment of IDD, novel polycaprolactone (PCL) nano fibers loaded with low-dose celecoxib were fabricated for IDD treatment. In vitro studies demonstrated that the nano fibers had the ability of releasing low-dose celecoxib slowly and sustainably and maintain PGE2. Meanwhile, in a puncture-induced rabbit IDD model, the nano fibers reversed IDD. Furthermore, low-dose celecoxib released from the nano fibers was firstly proved to promote CHSY3 expression. In a lumbar spine instability-induced mouse IDD model, low-dose celecoxib inhibited IDD in CHSY3wt mice rather than CHSY3−/− mice. This model indicated that CHSY3 was indispensable for low-dose celecoxib to alleviate IDD. In conclusion, this study developed a novel low-dose celecoxib-loaded PCL nano fibers to reverse IDD by maintaining PGE2 at the physiological level and promoting CHSY3 expression. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a malignant cancer worldwide. Long non-coding RNAs (lncRNAs) have emerged as key players in the development and progression of NSCLC, and may be potential biomarkers of NSCLC. Here, we investigated the clinical significance of lncRNA oxidative stress responsive serine rich 1 antisense RNA 1 (OSER1-AS1) in peripheral blood of patients with NSCLC. OSER1-AS1 in peripheral blood of patients with lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and healthy subjects was detected, and the clinical diagnostic efficacy was analyzed. The correlation between OSER1-AS1 expression and clinicopathological features in patients with LUSC and LUAD was analyzed. The downstream mechanism of OSER1-AS1 was explored. The area under the ROC curve of lncRNA OSER1-AS1 and miR-1298-5p/CHSY3 in LUSC and LUAD was compared using the MedCalc analysis. OSER1-AS1 was low in peripheral blood of patients with LUSC and LUAD. The area under the ROC curve for predicting LUSC was 0.800. The area under the ROC curve for predicting LUAD was 0.728. In LUSC and LUAD, OSER1-AS1 deficiency was associated with tumor node metastasis stage, lymph node metastasis, distal metastasis, and poor prognosis. miR-1298-5p was highly expressed, while chondroitin sulfate synthase 3 (CHSY3) was lowly expressed in patients with LUSC and LUAD. miR-1298-5p had target relations with OSER1-AS1 and CHSY3. lncRNA OSER1-AS1 had a higher diagnostic value in patients with NSCLC than miR-1298-5p and CHSY3. Overall, low expression of OSER1-AS1 in peripheral blood of NSCLC patients has high clinical significance, which provides a certain reference value for NSCLC early diagnosis. [ABSTRACT FROM AUTHOR]

Background: Chondroitin sulphate synthase 3 (CHSY3) is an important enzyme that regulates glycosylation, but it has not been reported in tumours. This study explored for the first time the oncological features of CHSY3 in stomach adenocarcinoma (STAD). Methods: We analysed CHSY3 expression in STAD through the Cancer Genome Atlas (TCGA) database and verified our findings by immunohistochemical staining and Western blot experiments. The prognostic value of CHSY3 in STAD was analysed through the biological aspects of CHSY3 in STAD, such as communal clinical follow-up survival data, methylation sites, tumour immune microenvironment (TIME) and immune cell surface checkpoints. Finally, the immune-evasion potential of CHSY3 in STAD was assessed on the Tumor Immune Dysfunction and Exclusion (TIDE) website and immunohistochemical staining experiment. Results: CHSY3 overexpression in STAD was associated with a poor prognosis based on immunohistochemical staining and Western blot experiments. Multivariate Cox analysis suggested that CHSY3 could be an independent prognostic risk factor. Pathway enrichment and TIME analysis demonstrated that CHSY3 up-regulated mesenchymal activation and immune activation signals in STAD, while TIDE assessment revealed that the risk of immune evasion was significantly higher in the high CHSY3 expression group than in the low CHSY3 expression group. Risk model scores based on CHSY3 -associated immune cell surface checkpoints also presented poor prognosis, and immune evasion was significantly higher in the high-risk group than in the low-risk group. Conclusions: This study analysed CHSY3 from multiple biological perspectives and revealed that CHSY3 can be a biomarker of poor prognosis and mediates the TIME immune-evasion status in STAD. [ABSTRACT FROM AUTHOR]