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
Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional p...Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.展开更多
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖...目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖和迁移的影响;4D-label free定量蛋白质组学分析挖掘As_(2)S_(2)抗TNBC的潜在干预靶点酸性核磷蛋白家族成员32A(acidic nuclear phosphoprotein family member 32A,ANP32A);慢病毒感染法构建ANP32A过表达敲低细胞株,探究潜在靶点ANP32A对As_(2)S_(2)抗TNBC作用的影响;蛋白质免疫共沉淀和Western blot实验探究As_(2)S_(2)是否通过ANP32A调控TNBC细胞H3乙酰化。结果As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A影响甚微,但显著抑制TNBC细胞增殖和迁移,且呈剂量依赖性;4D-lable free定量蛋白质组学分析结果显示,促癌因子ANP32A被As_(2)S_(2)显著下调,且ANP32A表达影响As_(2)S_(2)在TNBC中的抗增殖和迁移效果。As_(2)S_(2)能下调ANP32A的蛋白水平,抑制乙酰转移酶抑制剂复合物亚基的招募,增加H3乙酰化水平。结论As_(2)S_(2)通过下调ANP32A蛋白调控TNBC细胞中H3乙酰化,抑制TNBC细胞增殖和迁移。展开更多
目的探讨嗅觉受体家族13亚家族C成员2(olfactory receptor family 13 subfamily C member 2,OR13C2)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及临床病理意义。方法收集2017年8月至2022年3月于右江民族医学院附属医院进行手术...目的探讨嗅觉受体家族13亚家族C成员2(olfactory receptor family 13 subfamily C member 2,OR13C2)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及临床病理意义。方法收集2017年8月至2022年3月于右江民族医学院附属医院进行手术切除治疗的HCC患者为研究对象,取石蜡包埋的癌组织及癌旁非癌肝组织适量,采用免疫组化染色EnVision二步法检测OR13C2在上述组织中的表达情况,通过Logistic回归模型分析OR13C2的表达与HCC组织学分级、癌旁肝纤维化等临床病理特征的相关性。结果OR13C2在HCC癌组织中的表达明显低于癌旁肝组织,差异具有统计学意义(P<0.05);HCC肿瘤组织中OR13C2的表达与HCC组织学分级差异有统计学意义(P<0.05),HCC中OR13C2的表达与HCC的组织学分级呈负相关(r=-0.213,P<0.05),OR13C2表达下调为肿瘤去分化风险因子(风险值为3.914,P<0.05);OR13C2在癌组织中的表达与HCC的发病年龄、性别、包膜侵犯、临床分期、乙型肝炎病毒感染、术前血清甲胎蛋白及微血管侵犯以及癌组织中Glypican-3、Arginase-1表达的差异均无统计学意义(P>0.05),OR13C2在癌旁肝组织中的表达与肝纤维化分期、慢性肝炎分级差异无统计学意义(P>0.05)。结论HCC癌组织中OR13C2表达水平下调,这种下调与肿瘤的组织学分级负相关,是一个肿瘤去分化的风险因子。这些结果提示OR13C2表达失调在HCC发生中可能起一定的促进作用。展开更多
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jointly funded by projects supported by the National Natural Science Foundation of China(Grant No.41872150)the Joint Funds of the National Natural Science Foundation of China(Grant No.U19B6003)Major Scientific and Technological Projects of CNPC during the 13th five-year plan(No.2019A-02-10)。
文摘Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
文摘目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖和迁移的影响;4D-label free定量蛋白质组学分析挖掘As_(2)S_(2)抗TNBC的潜在干预靶点酸性核磷蛋白家族成员32A(acidic nuclear phosphoprotein family member 32A,ANP32A);慢病毒感染法构建ANP32A过表达敲低细胞株,探究潜在靶点ANP32A对As_(2)S_(2)抗TNBC作用的影响;蛋白质免疫共沉淀和Western blot实验探究As_(2)S_(2)是否通过ANP32A调控TNBC细胞H3乙酰化。结果As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A影响甚微,但显著抑制TNBC细胞增殖和迁移,且呈剂量依赖性;4D-lable free定量蛋白质组学分析结果显示,促癌因子ANP32A被As_(2)S_(2)显著下调,且ANP32A表达影响As_(2)S_(2)在TNBC中的抗增殖和迁移效果。As_(2)S_(2)能下调ANP32A的蛋白水平,抑制乙酰转移酶抑制剂复合物亚基的招募,增加H3乙酰化水平。结论As_(2)S_(2)通过下调ANP32A蛋白调控TNBC细胞中H3乙酰化,抑制TNBC细胞增殖和迁移。
文摘目的探讨嗅觉受体家族13亚家族C成员2(olfactory receptor family 13 subfamily C member 2,OR13C2)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及临床病理意义。方法收集2017年8月至2022年3月于右江民族医学院附属医院进行手术切除治疗的HCC患者为研究对象,取石蜡包埋的癌组织及癌旁非癌肝组织适量,采用免疫组化染色EnVision二步法检测OR13C2在上述组织中的表达情况,通过Logistic回归模型分析OR13C2的表达与HCC组织学分级、癌旁肝纤维化等临床病理特征的相关性。结果OR13C2在HCC癌组织中的表达明显低于癌旁肝组织,差异具有统计学意义(P<0.05);HCC肿瘤组织中OR13C2的表达与HCC组织学分级差异有统计学意义(P<0.05),HCC中OR13C2的表达与HCC的组织学分级呈负相关(r=-0.213,P<0.05),OR13C2表达下调为肿瘤去分化风险因子(风险值为3.914,P<0.05);OR13C2在癌组织中的表达与HCC的发病年龄、性别、包膜侵犯、临床分期、乙型肝炎病毒感染、术前血清甲胎蛋白及微血管侵犯以及癌组织中Glypican-3、Arginase-1表达的差异均无统计学意义(P>0.05),OR13C2在癌旁肝组织中的表达与肝纤维化分期、慢性肝炎分级差异无统计学意义(P>0.05)。结论HCC癌组织中OR13C2表达水平下调,这种下调与肿瘤的组织学分级负相关,是一个肿瘤去分化的风险因子。这些结果提示OR13C2表达失调在HCC发生中可能起一定的促进作用。
