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DHCR7 is a rate-limiting enzyme in cholesterol synthesis. The expression pattern and prognostic value of DHCR7 in cervical cancer are unknown. We investigated the relationship between DHCR7 expression and clinicopathological features of cervical cancer patients. The dataset was acquired from TCGA database. The Wilcoxon rank sum test was used to explore DHCR7 expression level in cervical cancer. The Kruskal-Wallis test and the logistic regression were performed to estimate the association between the DHCR7 and clinical features. The Kaplan-Meier and Cox regression analyses were used to evaluate factors that affect cervical cancer prognosis. GSEA was used to screen the DHCR7-related pathways. We found that DHCR7 was increased in cervical cancer samples and increased DHCR7 was correlated with advanced T stage, lymph node invasion, and clinical stage ( P < 0.05 ). Patients with elevated DHCR7 levels had poorer overall survival ( P = 0.021 ), progression-free interval ( P = 0.002 ), and disease-specific survival ( P = 0.005 ). Cox analysis revealed that DHCR7 was an independent prognostic factor in cervical cancer ( P = 0.005 ). WNT activated receptor activity, G2/M checkpoint, mTORC1 signaling, KRAS signaling, regulation of cholesterol biosynthetic, FGF signaling, T-cell receptor signaling, JAK/STAT signaling cascade T cell activation, and macrophage migration were enriched in high DHCR7 phenotype. Our data also showed that DHCR7 moderately correlates with T-cell infiltration, including CD8+ T-cells. Conclusion. Increased DHCR7 expression is associated with poor survival in cervical cancer.

Background:High-intensity interval training (HIIT) reportedly improves bone metabolism and increases bone mineral density (BMD). The purpose of the present study was to investigate whether lactate mediates the beneficial effects of exercise on BMD, bone microarchitecture, and biomechanical properties in an established osteoporotic animal model. In addition, we hypothesized that lactate-induced bone augmentation is achieved through enhanced osteoblast differentiation and mineralization.Methods:A total of 50 female C57BL/6 mice were randomly allocated into 5 groups: the nonovariectomized group, the ovariectomized group (OVX), the HIIT group (OVX + HIIT), the HIIT with lactate transporter inhibition group (OVX + HIIT + INH), and the lactate subcutaneous injection group (OVX + LAC). After 7 weeks of intervention, bone mass, bone strength, and bone formation/resorption processes were evaluated via microcomputed tomography (micro-CT), biomechanical testing, histological analysis, and serum biochemical assays; in vitro studies were performed to explore the bone anabolic effect of lactate at the cellular level.Results:Micro-CT revealed significantly increased BMD in both the OVX + HIIT group (mean difference, 41.03 mg hydroxyapatite [HA]/cm3 [95% CI, 2.51 to 79.54 mg HA/cm3]; p = 0.029) and the OVX + LAC group (mean difference, 40.40 mg HA/cm3 [95% CI, 4.08 to 76.71 mg HA/cm3]; p = 0.031) compared with the OVX group. Biomechanical testing demonstrated significantly improved mechanical properties in those 2 groups. However, the beneficial effects of exercise on bone microstructure and biomechanics were largely abolished by blocking the lactate transporter. Notably, histological and biochemical results indicated that increased bone formation was responsible for the bone augmentation effects of HIIT and lactate. Cell culture studies showed a marked increase in the expression of osteoblastic markers with lactate treatment, which could be eliminated by blocking the lactate transporter.Conclusions:Lactate may have mediated the bone anabolic effect of HIIT in osteoporotic mice, which may have resulted from enhanced osteoblast differentiation and mineralization.Clinical Relevance:Lactate may mediate the bone anabolic effect of HIIT and serve as a potential inexpensive therapeutic strategy for bone augmentation.

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