BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become anoth...BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.展开更多
BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promi...BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promise in gastric cancer.Its effects include promoting cell apoptosis,curtailing tumor angiogenesis,and enhancing sensitivity to radiation and chemotherapy.Long noncoding RNAs(lncRNAs)have garnered significant attention as biomarkers for early screening,diagnosis,treatment,and drug response because of their remarkable specificity and sensitivity.Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis,clinical staging,metastasis,drug sensitivity,and prognosis in gastric cancer.A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer develop-ment can provide novel insights for precision treatment and tailored management of patients with gastric cancer.This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregu-lating specific lncRNAs and modulating gastric cancer onset and progression.AIM To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis,proliferation,and invasion.Furthermore,these findings were validated in clinical samples.METHODS The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation,flow cytometry to investigate its effects on apoptosis,and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells.Western blotting was used to gauge changes in the protein expression levels of CDK6,CDK4,Bax,Bcl-2,caspase-3,P65,and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment.Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction(qRT-PCR)in BGC-823 and MGC-803 cells.AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis,proliferation,migration,and invasion of gastric cancer cells.Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways.RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics.RESULTS Curcumin induced apoptosis and hindered proliferation,migration,and invasion of gastric cancer cells in a dose-and time-dependent manner.LncRNA AC022424.2 was upregulated after curcumin treatment,and its knockdown enhanced cancer cell aggressiveness.LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways.LncRNA AC022424.2 downregulation was correlated with lymph node metastasis,making it a potential diagnostic and prognostic marker.CONCLUSION Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2.This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation.The results of this study enhance our understanding of gastric cancer development and precision treatment.展开更多
BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify geno...BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.展开更多
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivo...This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.展开更多
目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照...目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照组、MCAO组和MCAO+THSWD组各获得3个大脑半球组织。采用RNA测序技术鉴定三组中的lncRNA基因表达。鉴定了THSWD调节的lncRNA基因,然后构建了THSWD调节的lncRNA-mRNA网络。通过MCODE插件鉴定lncRNA-mRNA网络的模块。基因本体(gene ontology,GO)和京都基因与基因组百科全书数据库(kyoto encyclopedia of genes and genomes,KEGG)用于分析富集的生物功能和信号通路。鉴定了THSWD调节的lncRNA的顺式和反式调控基因。采用逆转录实时定量聚合酶链式反应(RT-qPCR)验证lncRNA。分子对接用于验证lncRNA-mRNA网络靶点和通路相关蛋白结合能力。结果在MCAO大鼠中,THSWD共调节了302个lncRNA。生物信息学分析表明,一些核心lncRNA可能在THSWD治疗MCAO大鼠中发挥重要作用,此外,我们进一步发现THSWD可能也通过lncRNA-mRNA网络以及网络富集的补体和凝血级联反应等多通路治疗MCAO大鼠。分子对接结果表明,THSWD活性化合物没食子酸和苦杏仁苷与蛋白质靶点具有一定的结合能力。结论THSWD可以通过调节lncRNA保护MCAO大鼠脑损伤,为THSWD治疗缺血性中风提供了新见解。展开更多
基金Supported by the Natural Science Funds for Young Scholar of Hebei,China,No.H2020206108the Subject of Health Commission of Hebei,China,No.20210151.
文摘BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.
基金Supported by the Natural Science Foundation of Gansu Province,China,No.20JR5RA356 and No.22JR5RA511the Lanzhou City Chengguan District Science and Technology Planning Project,No.2016-7-17.
文摘BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promise in gastric cancer.Its effects include promoting cell apoptosis,curtailing tumor angiogenesis,and enhancing sensitivity to radiation and chemotherapy.Long noncoding RNAs(lncRNAs)have garnered significant attention as biomarkers for early screening,diagnosis,treatment,and drug response because of their remarkable specificity and sensitivity.Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis,clinical staging,metastasis,drug sensitivity,and prognosis in gastric cancer.A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer develop-ment can provide novel insights for precision treatment and tailored management of patients with gastric cancer.This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregu-lating specific lncRNAs and modulating gastric cancer onset and progression.AIM To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis,proliferation,and invasion.Furthermore,these findings were validated in clinical samples.METHODS The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation,flow cytometry to investigate its effects on apoptosis,and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells.Western blotting was used to gauge changes in the protein expression levels of CDK6,CDK4,Bax,Bcl-2,caspase-3,P65,and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment.Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction(qRT-PCR)in BGC-823 and MGC-803 cells.AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis,proliferation,migration,and invasion of gastric cancer cells.Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways.RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics.RESULTS Curcumin induced apoptosis and hindered proliferation,migration,and invasion of gastric cancer cells in a dose-and time-dependent manner.LncRNA AC022424.2 was upregulated after curcumin treatment,and its knockdown enhanced cancer cell aggressiveness.LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways.LncRNA AC022424.2 downregulation was correlated with lymph node metastasis,making it a potential diagnostic and prognostic marker.CONCLUSION Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2.This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation.The results of this study enhance our understanding of gastric cancer development and precision treatment.
文摘BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
文摘This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.
文摘目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照组、MCAO组和MCAO+THSWD组各获得3个大脑半球组织。采用RNA测序技术鉴定三组中的lncRNA基因表达。鉴定了THSWD调节的lncRNA基因,然后构建了THSWD调节的lncRNA-mRNA网络。通过MCODE插件鉴定lncRNA-mRNA网络的模块。基因本体(gene ontology,GO)和京都基因与基因组百科全书数据库(kyoto encyclopedia of genes and genomes,KEGG)用于分析富集的生物功能和信号通路。鉴定了THSWD调节的lncRNA的顺式和反式调控基因。采用逆转录实时定量聚合酶链式反应(RT-qPCR)验证lncRNA。分子对接用于验证lncRNA-mRNA网络靶点和通路相关蛋白结合能力。结果在MCAO大鼠中,THSWD共调节了302个lncRNA。生物信息学分析表明,一些核心lncRNA可能在THSWD治疗MCAO大鼠中发挥重要作用,此外,我们进一步发现THSWD可能也通过lncRNA-mRNA网络以及网络富集的补体和凝血级联反应等多通路治疗MCAO大鼠。分子对接结果表明,THSWD活性化合物没食子酸和苦杏仁苷与蛋白质靶点具有一定的结合能力。结论THSWD可以通过调节lncRNA保护MCAO大鼠脑损伤,为THSWD治疗缺血性中风提供了新见解。
