ABSTRACT
Tripartite motif containing protein 7 (TRIM7), as a member of the E3 ubiquitin ligase TRIM family, plays an important regulatory role in immune regulation, metabolism and other physiological processes. The aberrant expression of TRIM7 is closely related to the development and progression of hepatocellular carcinoma (HCC) and it shows a complex regulatory role. However, the regulatory mechanism for the expression of TRIM7 in HCC remains unknown. In this study, multiple online databases were used to analyze the expression of TRIM7 in HCC and data indicated that TRIM7 expression was upregulated in HCC and correlated to poor prognosis. Subsequently, the transcription factor binding sites in the TRIM7 promoter region were analyzed using UCSC and JASPAR databases, and the results showed that TRIM7 promoter contains four SP1 binding sites. In this work, we demonstrated that SP1 could directly bind to its binding sites in TRIM7 promoter and positively regulate the transcriptional activity driven by the TRIM7 promoter using dual luciferase reporter experiments and the ChIP-PCR method. Moreover, our results also showed SP1 overexpression upregulated the expression of TRIM7 at both mRNA and protein levels (P<0. 01),and SP1 inhibitor, mithramycin A, could reverse the activated effect of SP1 on TRIM7 expression (P<0. 01). In conclusion, this study preliminarily reveals the regulatory mechanism of TRIM7 upregulation in HCC, which provides an important theoretical basis for further study of the gene function, early diagnosis and targeted therapy.
ABSTRACT
OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people, could not be prevented, halted, or reversed up till now. A large body of pharmacological study has revealed that Liuwei Dihuang (LW) possesses potential therapeutic effects on AD. LW-AFC is key fractions from LW.In the present study,we investigated the effect of LW-AFC on AD mouse models. METHODS PrP-hAβPPswe/PS1ΔE9(APP/PS1) mice and senescence-accelerated mouse prone 8 strain (SAMP8), classic AD animal models, were employed. After the treatment of LW-AFC, mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β (Αβ) deposition, and Αβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using fl ow cytometry. RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1and SAMP8 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed amyloid-β(Αβ)deposition in the brain,and reduced the concentration of Aβ1-42in the hippo-campus and plasma of APP/PS1 mice. LW-AFC treatment also significantly restored the imbalance of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis, enhanced the proliferation of splenocytes,corrected the disorder of lymphocyte subsets,and regulated the abnormal production of cytokine in APP/PS1 and SAMP8 mice. Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in APP/PS1 and SAMP8 mice were better than meman-tine and donepezil. CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of AD mouse models via the restoration of the NIM network, which supports the use of LW-AFC as a potential agent for AD therapy.