2 research outputs found
MIOX inhibits autophagy to regulate the ROS -driven inhibition of STAT3/c-Myc-mediated epithelial-mesenchymal transition in clear cell renal cell carcinoma
The specific mechanism of clear cell renal cell carcinoma (ccRCC) progression, a pathological type that accounts for the highest proportion of RCC, remains unclear. In this study, bioinformatics analysis of scRNA-seq dataset in ccRCC revealed that MIOX was a gene specifically down-regulated in tumor epithelial cells of ccRCC. Analysis of the TCGA database further validated the association between decreased MIOX mRNA levels and ccRCC malignant phenotype and poor prognosis. Immunohistochemistry indicated the down-regulation of MIOX in ccRCC tissues compared to paired adjacent renal tissues, with further down-regulation of MIOX in the primary tumors of patients with primary metastasis compared to those without metastasis. Also, patients with low expression of MIOX showed shorter metastasis-free survival (MFS) compared to those with high MIOX expression. In vitro results showed that overexpression of MIOX in ccRCC cells inhibited the proliferation, migration and invasion and promoted apoptosis. Mechanistically, up-regulation of MIOX inhibited autophagy to elevate the levels of ROS, and thus suppressed STAT3/c-Myc-mediated epithelial-mesenchymal transition in ccRCC cells. In vivo data further confirmed that increased MIOX expression suppressed the growth and proliferation of RCC cells and reduced the ability of RCC cells to form metastases in the lung. This study demonstrates that MIOX is an important regulatory molecule of ccRCC, which is conducive to understanding the potential molecular mechanism of ccRCC progression
Reactive Oxygen Species- and Cell-Free DNA-Scavenging Mn<sub>3</sub>O<sub>4</sub> Nanozymes for Acute Kidney Injury Therapy
Reactive
oxygen species (ROS) scavenging therapy toward
acute kidney
injury (AKI) is promising, but no effective ROS scavenging drug has
been developed yet. Moreover, cell-free DNA (cfDNA) is also involved
in AKI, but the corresponding therapies have not been well developed.
To tackle these challenges, Mn3O4 nanoflowers
(Nfs) possessing both ROS and cfDNA scavenging activities were developed
for better AKI protection as follows. First, Mn3O4 Nfs could protect HK2 cells through cascade ROS scavenging (dismutating ·O2– into H2O2 by superoxide dismutase-like activity and then decomposing
H2O2 by catalase-like activity). Second, Mn3O4 Nfs could efficiently adsorb cfDNA and then
decrease the inflammation caused by cfDNA. Combined, remarkable therapeutic
efficacy was achieved in both cisplatin-induced and ischemia–reperfusion
AKI murine models. Furthermore, Mn3O4 Nfs could
be used for the T1-MRI real-time imaging
of AKI. This study not only offered a promising treatment for AKI
but also showed the translational potential of nanozymes