Recent exploration results indicate that a significant exploration potential remains in the Dongying Depression of the Bohai Bay Basin and the undiscovered oil and gas are largely reservoired in subtle traps including...Recent exploration results indicate that a significant exploration potential remains in the Dongying Depression of the Bohai Bay Basin and the undiscovered oil and gas are largely reservoired in subtle traps including turbidite litholigcal traps of the Sha-3 Member. In order to effectively guide the exploration program targeting turbidites, this study will focus on the depositional models of the Sha-3 Member turbidites and oil/gas accumulation characteristics in these turbidites. Two corresponding relationships were found. One is that the East African Rift Valley provides a modern analog for the depositional systems in the Dongying Depression. The other is that the depositional models of line-sourced slope aprons, single point-source submarine fan and multiple source ramp turbidite, established for deep-sea turbidites, can be applied to interpret the depositional features of the turbidite fans of three different origins: slope turbidite aprons, lake floor turbidite fans and delta-fed turbidite fans in the Sha-3 Member. Updip sealing integrity is the key factor determining whether oil/gas accumulates or not in the slope aprons and lake floor fans. The factors controlling oil/gas migration and accumulation in the delta-fed turbidite fans are not very clear. Multiple factors rather than a single factor probably played significant roles in these processes.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
BACKGROUND Vestigial like family member 3(VGLL3)is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma,but its role in gastric cancer(GC)is unclear.AIM To explore the expression pattern ...BACKGROUND Vestigial like family member 3(VGLL3)is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma,but its role in gastric cancer(GC)is unclear.AIM To explore the expression pattern and clinical significance of VGLL3 in GC.METHODS Integrative analysis was performed on the GC transcriptome profiles and survival information deposited in the ONCOMINE,GEPIA,and ONCOLNC databases.The expression levels of VGLL3 mRNA and protein were analyzed in the freshly resected tumor and normal gastric tissues from GC patients by quantitative RT-PCR and Western blot,respectively.In addition,the in situ expression of VGLL3 in the GC tissues was determined by immunohistochemistry(IHC),and the patients were accordingly classified into the high and low expression groups.The correlation of VGLL3 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.RESULTS Analysis of the ONCOMINE and GEPIA databases showed that VGLL3 was significantly up-regulated in GC tissues(P=0.003),and associated with the tumor TNM stage(P=0.0163).The high VGLL3 expression group had a significantly worse prognosis compared to the low expression group,as per both GEPIA(P=0.0057)and ONCOLNC(P=0.01).The bioinformatics results were validated by the significantly higher VGLL3 mRNA and protein levels in the GC tissues compared to the adjacent normal tissues(P<0.001)in a cohort of 30 GC patients.Furthermore,high in situ expression of VGLL3 protein was associated with more advanced N and TNM stages and HER2 mutation(P<0.05)in a cohort of 172 patients.Kaplan-Meier analysis showed that the high VGLL3 expression group had a worse prognosis compared to the low expression group(P=0.019).Multivariate analysis showed that VGLL3 expression status was an independent risk factor for prognosis.In addition,the prognostic risk model nomogram showed that VGLL3 was the most important indicator,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.613 for 3-year survival and 0.706 for 5-year survival.Finally,the protein interaction network analysis revealed that VGLL3 is likely involved in the Hippo signaling pathway.CONCLUSION VGLL3 is overexpressed in GC tissues and associated with a poor prognosis,indicating its potential as a novel prognosis biomarker and therapeutic target for GC.展开更多
文摘Recent exploration results indicate that a significant exploration potential remains in the Dongying Depression of the Bohai Bay Basin and the undiscovered oil and gas are largely reservoired in subtle traps including turbidite litholigcal traps of the Sha-3 Member. In order to effectively guide the exploration program targeting turbidites, this study will focus on the depositional models of the Sha-3 Member turbidites and oil/gas accumulation characteristics in these turbidites. Two corresponding relationships were found. One is that the East African Rift Valley provides a modern analog for the depositional systems in the Dongying Depression. The other is that the depositional models of line-sourced slope aprons, single point-source submarine fan and multiple source ramp turbidite, established for deep-sea turbidites, can be applied to interpret the depositional features of the turbidite fans of three different origins: slope turbidite aprons, lake floor turbidite fans and delta-fed turbidite fans in the Sha-3 Member. Updip sealing integrity is the key factor determining whether oil/gas accumulates or not in the slope aprons and lake floor fans. The factors controlling oil/gas migration and accumulation in the delta-fed turbidite fans are not very clear. Multiple factors rather than a single factor probably played significant roles in these processes.
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
基金Supported by the Natural Science Foundation of Jiangsu Province,No.BK20171150the National Natural Science Foundation of China,No.81502042+1 种基金Research Project of Health and Family Planning Commission of Wuxi,No.Q201758Nanchang Hongda Jianghua Educational Foundation
文摘BACKGROUND Vestigial like family member 3(VGLL3)is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma,but its role in gastric cancer(GC)is unclear.AIM To explore the expression pattern and clinical significance of VGLL3 in GC.METHODS Integrative analysis was performed on the GC transcriptome profiles and survival information deposited in the ONCOMINE,GEPIA,and ONCOLNC databases.The expression levels of VGLL3 mRNA and protein were analyzed in the freshly resected tumor and normal gastric tissues from GC patients by quantitative RT-PCR and Western blot,respectively.In addition,the in situ expression of VGLL3 in the GC tissues was determined by immunohistochemistry(IHC),and the patients were accordingly classified into the high and low expression groups.The correlation of VGLL3 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.RESULTS Analysis of the ONCOMINE and GEPIA databases showed that VGLL3 was significantly up-regulated in GC tissues(P=0.003),and associated with the tumor TNM stage(P=0.0163).The high VGLL3 expression group had a significantly worse prognosis compared to the low expression group,as per both GEPIA(P=0.0057)and ONCOLNC(P=0.01).The bioinformatics results were validated by the significantly higher VGLL3 mRNA and protein levels in the GC tissues compared to the adjacent normal tissues(P<0.001)in a cohort of 30 GC patients.Furthermore,high in situ expression of VGLL3 protein was associated with more advanced N and TNM stages and HER2 mutation(P<0.05)in a cohort of 172 patients.Kaplan-Meier analysis showed that the high VGLL3 expression group had a worse prognosis compared to the low expression group(P=0.019).Multivariate analysis showed that VGLL3 expression status was an independent risk factor for prognosis.In addition,the prognostic risk model nomogram showed that VGLL3 was the most important indicator,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.613 for 3-year survival and 0.706 for 5-year survival.Finally,the protein interaction network analysis revealed that VGLL3 is likely involved in the Hippo signaling pathway.CONCLUSION VGLL3 is overexpressed in GC tissues and associated with a poor prognosis,indicating its potential as a novel prognosis biomarker and therapeutic target for GC.
