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| 1 | Small-molecule inhibitor LF3 restrains the development of pulmonary hypertension through the Wnt/β-catenin pathway显示文摘Pulmonary hypertension(PH)associated with congenital heart disease is a progressive hemodynamic disease that can lead to increased pulmonary vascular resistance,vascular remodeling,and even right heart failure and death.LF3 is a novel inhibitor of the reporter gene activity ofβ-catenin/TCF4 interaction in the Wnt/β-catenin signal pathway.However,whether this action of LF3 can prevent PH development remains unclear.In this study,we investigated the therapeutic effect of LF3 in rat primary pulmonary artery smooth muscle cells(PASMCs)of the PH model.We found that LF3 inhibited the decrease in pulmonary artery acceleration time and ejection time by ultra-high-resolution ultrasound imaging and blocked the increase of pulmonary artery systolic pressure by using the BL420 biological function experimental system and right ventricular hypertrophy index by the electronic scales.Simultaneously,it prevented the increase ofα-smooth muscle actin and fibronectin and the decrease of elastin in pulmonary arteries of rats in the PH group,as revealed by an immunohistochemical analysis.Moreover,cell proliferation and migration assays showed that LF3 significantly reduced the proliferation and migration of PASMCs.Western blotting and quantitative real-time polymerase chain reaction analyses revealed that LF3 suppressed the expression of proliferating cell nuclear antigens and Bcl-2 and increased the expression of Bax but did not alter the expressions ofβ-catenin and TCF4.Taken together,LF3 can reduce the migration and proliferation of PASMCs and induce their apoptosis to prevent the development of PH.It would be worthwhile to explore the potential use of LF3 in the treatment of PH. | Yong Lei Qi Yang Yongmei Nie Juyi Wan Mingbin Deng | 2021 | Acta Biochimica et Biophysica Sinica2021，53，10： | 2 |
| 2 | Prognostic Role and Potential Mechanisms of N6-methyladenosine-related Long Noncoding RNAs in Hepatocellular Carcinoma显示文摘Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we systematically analyzed the role and prognostic value of m^(6)A-related lncRNAs in hepatocellular carcinoma(HCC).Methods:The m^(6)A-related lncRNAs were identified based on the correlation coefficients with m^(6)A-related genes in HCC from The Cancer Genome Atlas.Subsequently,a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses.Univariate and multivariate Cox analyses were used to identify independent prog-nostic factors for overall survival(OS)of HCC;thereafter,a prognostic nomogram was constructed.Results:A total of 259 lncRNAs showed significant correlations with m^(6)A in HCC,while 29 lncRNAs had prognostic significance.Further,six critical m^(6)A-related lncRNAs(NRAV,SNHG3,KDM4A-AS1,AC074117.1,AC025176.1,and AL031985.3)were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups.Survival analy-ses revealed that patients in the high-risk group exhibited worse OS,both in the training and validation groups.The risk score was also identified as an independent prognostic factor of OS,and a nomogram was established and verified with superior prediction capacity.Besides,the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes.Conclusions:These findings indicated the significant role of m^(6)A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction. | Tianxing Dai Jing Li Linsen Ye Haoyuan Yu Mingbin Deng Wei Liu Hua Li Yang Yang Guoying Wang | 2022 | Journal of Clinical and Translational Hepatology2022，10，2： | 1 |
| 3 | Upregulation of TMCO3 Promoting Tumor Progression and Contributing to the Poor Prognosis of Hepatocellular Carcinoma显示文摘Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expression profile,prognostic significance,and oncogenic role of TMCO3 in hepatocellular carcinoma(HCC).Methods:Bioinformatic analyses were conducted using transcriptome data from public databases to determine the expression,prognosis,and functional enrichment of TMCO3 in HCC.TMCO3 expression was further validated in an independent HCC cohort from our institution.The oncogenic role of TMCO3 in HCC was evaluated using in vitro and in vivo experiments.Results:The upregulated expression of TMCO3 was identified and verified in multiple HCC cohorts,and worse overall survival and recurrence-free survival were observed in patients with high TMCO3 expression.The overexpression and knockdown of TMCO3 could affect the proliferation and metastasis of HCC cells,which might be associated with the p53-induced cell cycle regulation and epithelial-mesenchymal transition,respectively.Notably,significant correlations were found between dysregulated TMCO3 and various antitumor agents.Its role in sorafenib sensitivity was further identified by in vitro experiments and the potential mechanism might be related to the regulation of apoptosis.Positive correlations were also identified between upregulation of TMCO3 and the increased infiltration of various immune cells and the elevated expression of multiple immune checkpoint genes in HCC.Conclusions:Upregulated TMCO3 could act as an oncogenic mediator and promote sorafenib resistance in HCC,providing a potential therapeutic target for HCC treatment. | Tianxing Dai Linsen Ye Mingbin Deng Guozhen Lin Rongqiang Liu Haoyuan Yu Wei Liu Yang Yang Guoying Wang | 2022 | Journal of Clinical and Translational Hepatology2022，10，5： | 0 |
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