RESUMO
Objective: This study aimed to investigate the effects of long-term hypoxic environment exposure on cognitive ability and neuroimaging characteristics in a highland population in China. Methods: Health system workers in Maduo County (4,300 m above sea level) and Minhe County (1,700 m above sea level) were selected as research participants and divided into a high-altitude (HA) group and low-altitude (LA) group, respectively. Cognitive ability was assessed using the Montreal Cognitive Assessment (MoCA), Verbal Fluency Test (VFT), Symbol Digit Modalities Test (SDMT), Trail Making Test A and B (TMT), Digit Span Test (DST), and Rey Auditory Verbal Learning Test (RAVLT). All participants underwent a magnetic resonance imaging (MRI) scan, resting state functional MRI scan, and diffusion tensor imaging to clarify changes in regional gray matter (GM) volume, anisotropy index (FA), local consistency (ReHo), and low-frequency oscillation amplitude (ALFF). Results: The HA group had significantly lower MoCA, DST, VFT, RAVLT, and TMT scores compared to the control group. No significant differences were found in SDMT score. Furthermore, compared to the LA group, the HA group had significantly lower GM density of the left olfactory cortex, right medial orbital superior frontal gyrus, bilateral insula, left globus pallidus, and temporal lobe (left superior temporal gyrus temporal pole, bilateral middle temporal gyrus temporal pole, and right middle temporal gyrus). In terms of FA, compared with the LA group, the HA group had lower values for the corpus callosum, corpus callosum knee, bilateral radiative corona, and left internal capsule. The HA group had lower ALFF values of the left cerebellum, left putamen, left orbital inferior frontal gyrus, and left precuneus, but higher ALFF values of the left fusiform gyrus, bilateral inferior temporal gyrus, left orbital superior frontal gyrus and medial superior frontal gyrus, compared to the LA group. There was no significant group difference in ReHo values. Conclusion: Our findings suggest that a chronic hypoxic environment can induce extensive cognitive impairment. Decreased GM density in multiple brain regions, damaged nerve fibers, and unbalanced neuronal activity intensity in different brain regions may be the structural and functional basis of cognitive impairment due to hypoxia.
RESUMO
The ubiquitin-protein ligase E3C (UBE3C) belongs to the E3 ligase enzyme family and implicates in the ubiquitin-proteasome pathway, thus regulates physiological and cancer-related processes. Here, we investigated the expression and roles of UBE3C in glioma. We demonstrated that UBE3C was overexpressed in glioma tissues and cell lines. Inhibition of UBE3C expression in glioma cells significantly decreased cell migration and invasion in vitro. Mechanistically, we disclosed that UBE3C physically interacted with and ubiquitinated tumor suppressor gene annexin A7 (ANXA7), resulting in ubiquitination and degradation of ANXA7. Our results also revealed that increased UBE3C expression was accompanied by a reduction in ANXA7 protein expression in glioma tissues, but not ANXA7 mRNA. Importantly, the inhibition of ANXA7 expression in gliomas cells with UBE3C interference could rescue the cell invasion. Clinically, UBE3C overexpression significantly correlated with high-grade tumors (p < 0.05), poor overall survival, and early tumor recurrence. Thus, our data reveal that high UBE3C expression contributes to glioma progression by ubiquitination and degradation of ANXA7, and thus presents a novel and promising target for glioma therapy.
