The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.
Background:Immune checkpoint inhibitors (ICIs) have been proven to be beneficial in multiple advanced malignancies. However, the widespread use of ICIs also occurred with various immune-related adverse events (irAEs). However, while various immune-related adverse events related to immune checkpoint inhibitors have been reported, there are few reports of lower urinary tract symptoms. Case presentation:A 42-year-old woman with lung cancer who was being treated with sintilimab, anlotinib, and denosumab presented to the nephrology department with frequent micturition, urgency, odynuria and gross hematuria. Initial laboratory tests did not reveal bacteria, but CT examination suggested cystitis. After empiric antiinfective therapy, the above symptoms did not improve significantly. The patient stopped taking sinlizumab and completed cystoscopy. Based on the combined clinical manifestations and laboratory findings, he was diagnosed with immune-related cystitis. Symptomatic relief was achieved via steroid treatment. Thereafter, the patient has been followed for 3 months without any symptoms or recurrence of immune-related cystitis Conclusions: immune-related cystitis is a commonly misdiagnosed disease. However, early diagnosis, treatment and prophylaxis through accumulated clinical data can help patients achieve a good prognosis. Therefore, clinicians need to be well aware of the variety of clinical characteristics and treatment options of this disease.
In the current study, paclitaxel was loaded into electrospun gelatin nanofibers in order to produce a potential anti-cancer membrane. The developed system was studied for its cytotoxic effects against breast cancer MCF-7 cells. Furthermore, biodegradation rate, microstructure, cell migration assay, and tensile strength were performed for the evaluation of anticancer local therapeutic. Study showed that, the electrospun membranes were composed of smooth and web-like nanofibers. In addition, the paclitaxel-loaded nanofibers were toxic against breast cancer cells and prevented their migration. Real time PCR assay showed that the anticancer activity of the developed system might be through regulation of DJ-1/KLF 17 signalling pathway.
Background: Emerging evidences have indicated that microRNAs (miRNAs) play a significant role in multiple biological processes, including the control of the cell cycle, apoptosis, autophagy and metabolic reprogramming. Among them, miRNA-518a-3p has been revealed to display a notably key function during the development of many types of cancer, containing colorectal cancer, breast cancer and squamous cell carcinoma. However, its functions and the molecular mechanisms during HCC progression still remain unclear. Methods: miRNA-518a-3p expression level was detected by RT-qPCR in HCC tumor tissues and four HCC cell lines, and its related prognostic effects were also investigated. Furthermore, its functions during HCC progression were investigated by CCK-8 experiment, transwell assay in two HCC cell lines. Moreover, its potential mechanisms were investigated by bioinformatic analysis, RT-qPCR, western blotting, luciferase reporter assay and rescue experiments. Results: Downregulation of miRNA-518a-3p was found in HCC tumor tissues and correlated with a more awful overall survival. Gain and loss of function analyses displayed miRNA-518a-3p repressed HCC cells proliferation, migration and invasion. Then, bioinformatic analysis and luciferase reporter assay have suggested that ZNF281, upregulated in HCC tumor tissues, was negatively regulated by miRNA-518a-3p. Moreover, rescue experiments demonstrated that the suppression of HCC progression by miRNA-518a-3p was mediated by ZNF281.Conclusion: Our studies indicated that miRNA-518a-3p inhibited hepatocarcinogenesis through suppression of ZNF281 expression, indicating that miRNA-518a-3p is a promising therapeutic approach targeting for the treatment of HCC.
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