Glioblastoma multiforme(GBM),the most common and aggressive primary brain tumor in adults,is the most malignant and still has no cure.However,the novel role of long non-coding RNAs(lncRNAs)in the pathogenesis of gliob...Glioblastoma multiforme(GBM),the most common and aggressive primary brain tumor in adults,is the most malignant and still has no cure.However,the novel role of long non-coding RNAs(lncRNAs)in the pathogenesis of glioblastoma is attracting extensive attention.LncRNAs are transcribed RNA molecules over 200 nucleotides long that do not encode proteins.Unlike small non-coding RNAs,such as microRNAs(miRNAs),lncRNAs have more complex secondary and tertiary structures that enable them to interact with DNA,RNA,and proteins and perform multiple regulatory functions.LncRNAs act as molecular sponges,absorbing and sequestering other biomolecules,particularly miRNAs,thereby preventing these molecules from performing their normal functions.LncRNAs influence glioblastoma through gene expression regulation,molecular sponge capacity,epigenetic modulation,and signaling pathway interactions.In glioblastoma,a large number of lncRNAs have been found to be abnormally expressed,affecting tumor growth,invasion and resistance to treatment.Due to its regulatory role and disease-specific expression patterns,lncRNA has become a potential biomarker for glioblastoma and a promising new therapeutic target.This paper discusses the spongy role of lncRNAs in glioblastoma and its potential therapeutic applications,which will lay a foundation for our understanding of glioblastoma biology and the development of new diagnostic and therapeutic strategies in the future.展开更多
Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber,...Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber, type, and function of T cells in the tumor microenvironment (TME) determine the progression andtreatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development,and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigatewhether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified tofurther establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized byrobust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. Theexcellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort andthe GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-basednomogram, which had important clinical significance in estimating the survival probability for individuals. Inaddition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with highTRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade wassignificantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs couldunambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identifiedT cell-Lncs could provide potential therapeutic targets for LUAD.展开更多
Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the progn...Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.展开更多
Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data...Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data and RNA-seq of 443 GC cases were obtained from The Cancer Genome Atlas(TCGA)database,and CRLs were screened by Pearson analysis,Cox regression,and least absolute shrinkage and selection operator(LASSO)regression to construct a risk model to predict GC prognosis,and the nomogram was constructed by combining risk scores and clinical characteristics.The accuracy of the model was validated by the receiver operating characteristic curve,Kaplan-Meier curves and C-index.To assess the correlation of risk scores with immune infiltration,immune checkpoint gene expression and chemotherapy/targeted agents.The Coremine Medical database was applied to predict potential traditional Chinese medicine that regulate CRGs.Results:Risk models for GC were constructed based on the risk scores of seven CRLs(AP001107.9,VCAN-AS1,AC016394.2,LINC02675,AC100814.1,HAGLR,and LINC01094).The AUC of the risk model predicting 1-,3-,and 5-year survival in GC patients was 0.720,0.682,and 0.711,and its prognostic value was better than age,Grade classification,and TNM stage.The AUC of the risk model combining age and TNM stage to predict 1-year survival in GC patients was 0.793.The risk score correlated with the degree of enrichment of immune cells such as tumorinfiltrating lymphocytes and regulatory T cells and the expression of 22 immune checkpoint genes such as LAG3,ICOS,CD28,NRP1 and the sensitivity of 13 chemotherapeutic/targeted agents.There are 58 traditional Chinese medicine with potential regulatory effects on CRGs,mainly for clearing heat and detoxing,promoting blood circulation and relieving pain,which are mainly attributed to the liver,spleen and lung meridians.Spirulina and osthole have potential regulatory effects on FDX1,a key gene in the death mechanism of cuproptosis.Conclusions:A risk signature constructed based on seven CRLs could assess the prognosis and immunity of GC,and Spirulina and Serpentine may have important regulatory efficacy on the mechanism of copper cuproptosis.展开更多
Soybean mutants withα-nullβ-conglycinin are associated with high nutritional value and low allergenic risk.Although long noncoding RNAs(lncRNAs)are increasingly recognized as functional regulatory components affecti...Soybean mutants withα-nullβ-conglycinin are associated with high nutritional value and low allergenic risk.Although long noncoding RNAs(lncRNAs)are increasingly recognized as functional regulatory components affecting eukaryotic gene expression,little is known about lnc RNA profiles inα-null-type hypoallergenic soybeans.In this study,a genome-wide integrative analysis of lncRNAs,m RNAs and epigenomic data in the soybean cgy-2(confirmedα-null)near-isogenic line(NIL)and its recurrent parent Dongnong47(DN47)was conducted.Nineteen novel lncRNAs that were differentially expressed(DE)only in the NIL at 18 days after flowering(i.e.,α-null-associated DE lncRNAs)were delected.Sixteen putative soybean stress-responsive lncRNAs were identified,and observed to regulate 257 stress-related genes DE in the NIL.This result indicated that theα-null allele might represent an intrinsic defect stress that altered the expression of various stress-related genes inα-null-type hypoallergenic soybean.Additionally,25 epigenetic-related lncRNAs regulated 831 DE epigenetic-related genes and simultaneously initiated multiple epigenetic activities,including ubiquitination,methylation and acetylation.Kyoto encyclopedia of genes and genomes(KEGG)analysis indicated that the biosynthesis of amino acids pathway was enriched with 83 DE genes regulated by nine DE lncRNAs.Changes in the expression of these lncRNAs and genes might be the reason for the altered amino acid composition in the NIL.Among all detected DE lncRNAs,MSTRG.12518 was the most conspicuousα-null-specific cis/trans-lnc RNA that played an efficient,versatile and vital role in the NIL.The data indicated that the lnc RNA profile differed between the NIL and DN47.Variations in lncRNAs,gene expression levels and DNA methylation states likely contributed to the intrinsic defect stress response mechanism inα-null-type hypoallergenic soybeans.展开更多
Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and ...Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and neck squamous cell carcinoma(HNSCC).RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas.In the training group,we used Pearson correlation,univariate Cox regression,least absolute shrinkage/selection operator regression analyses,and multivariate Cox regression to build a prognostic model.In the test group,we evaluated the model.Multivariate Cox regression was done to screen out independent prognostic factors,with which we constructed a nomogram.Afterward,we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics.Gene set enrichment analysis,immune correlation analysis,and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.The most important LINC00861 in the model was examined in HNE1,CNE1,and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid.In addition,CCK-8,Edu,and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells.The signature based on nine ARLs has a good predictive value in survival time,immune infiltration,immune checkpoint expression,and sensitivity to multiple drugs.LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells,and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines.This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC.LINC00861 is a protective factor for the development of HNSCC.展开更多
基金The study is funded by Binzhou Medical University Research Fund Project(Grant Number BY2021KYQD02).
文摘Glioblastoma multiforme(GBM),the most common and aggressive primary brain tumor in adults,is the most malignant and still has no cure.However,the novel role of long non-coding RNAs(lncRNAs)in the pathogenesis of glioblastoma is attracting extensive attention.LncRNAs are transcribed RNA molecules over 200 nucleotides long that do not encode proteins.Unlike small non-coding RNAs,such as microRNAs(miRNAs),lncRNAs have more complex secondary and tertiary structures that enable them to interact with DNA,RNA,and proteins and perform multiple regulatory functions.LncRNAs act as molecular sponges,absorbing and sequestering other biomolecules,particularly miRNAs,thereby preventing these molecules from performing their normal functions.LncRNAs influence glioblastoma through gene expression regulation,molecular sponge capacity,epigenetic modulation,and signaling pathway interactions.In glioblastoma,a large number of lncRNAs have been found to be abnormally expressed,affecting tumor growth,invasion and resistance to treatment.Due to its regulatory role and disease-specific expression patterns,lncRNA has become a potential biomarker for glioblastoma and a promising new therapeutic target.This paper discusses the spongy role of lncRNAs in glioblastoma and its potential therapeutic applications,which will lay a foundation for our understanding of glioblastoma biology and the development of new diagnostic and therapeutic strategies in the future.
基金supported by the following funds:the Key Research and Development Project of the Science and Technology Department of Sichuan Province(Grant Nos.2021YFS0202 and 2021YFS0229)the Natural Science Foundation of Sichuan Province(Grant No.2022NSFSC1326)+1 种基金Postdoctoral Research Fund of West China Hospital(Grant Nos.2019HXBH056 and 2020HXBH066)China Postdoctoral Science Foundation(Grant No.2022T150454).
文摘Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber, type, and function of T cells in the tumor microenvironment (TME) determine the progression andtreatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development,and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigatewhether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified tofurther establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized byrobust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. Theexcellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort andthe GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-basednomogram, which had important clinical significance in estimating the survival probability for individuals. Inaddition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with highTRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade wassignificantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs couldunambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identifiedT cell-Lncs could provide potential therapeutic targets for LUAD.
基金supported by a grant Hebei Provincial Health Commission project from the Foundation of Basic Research(No.20191843).
文摘Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.
基金National Natural Science Foundation of China (81573959)Capital Health Development Research Special Project (2020-2-4193)。
文摘Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data and RNA-seq of 443 GC cases were obtained from The Cancer Genome Atlas(TCGA)database,and CRLs were screened by Pearson analysis,Cox regression,and least absolute shrinkage and selection operator(LASSO)regression to construct a risk model to predict GC prognosis,and the nomogram was constructed by combining risk scores and clinical characteristics.The accuracy of the model was validated by the receiver operating characteristic curve,Kaplan-Meier curves and C-index.To assess the correlation of risk scores with immune infiltration,immune checkpoint gene expression and chemotherapy/targeted agents.The Coremine Medical database was applied to predict potential traditional Chinese medicine that regulate CRGs.Results:Risk models for GC were constructed based on the risk scores of seven CRLs(AP001107.9,VCAN-AS1,AC016394.2,LINC02675,AC100814.1,HAGLR,and LINC01094).The AUC of the risk model predicting 1-,3-,and 5-year survival in GC patients was 0.720,0.682,and 0.711,and its prognostic value was better than age,Grade classification,and TNM stage.The AUC of the risk model combining age and TNM stage to predict 1-year survival in GC patients was 0.793.The risk score correlated with the degree of enrichment of immune cells such as tumorinfiltrating lymphocytes and regulatory T cells and the expression of 22 immune checkpoint genes such as LAG3,ICOS,CD28,NRP1 and the sensitivity of 13 chemotherapeutic/targeted agents.There are 58 traditional Chinese medicine with potential regulatory effects on CRGs,mainly for clearing heat and detoxing,promoting blood circulation and relieving pain,which are mainly attributed to the liver,spleen and lung meridians.Spirulina and osthole have potential regulatory effects on FDX1,a key gene in the death mechanism of cuproptosis.Conclusions:A risk signature constructed based on seven CRLs could assess the prognosis and immunity of GC,and Spirulina and Serpentine may have important regulatory efficacy on the mechanism of copper cuproptosis.
基金Supported by the National Natural Science Foundation of China(31801386,31371650)the Ministry of Science and Technology of China(2016YFD0100500)+2 种基金Funding from Harbin Science and Technology Bureau(2016RQYXJ018,2017RAQXJ104)Heilongjiang Natural Science Foundation(LC2018008)the Key Laboratory of Soybean Biology in the Chinese Ministry of Education,Northeast Agricultural University(SB17A01)。
文摘Soybean mutants withα-nullβ-conglycinin are associated with high nutritional value and low allergenic risk.Although long noncoding RNAs(lncRNAs)are increasingly recognized as functional regulatory components affecting eukaryotic gene expression,little is known about lnc RNA profiles inα-null-type hypoallergenic soybeans.In this study,a genome-wide integrative analysis of lncRNAs,m RNAs and epigenomic data in the soybean cgy-2(confirmedα-null)near-isogenic line(NIL)and its recurrent parent Dongnong47(DN47)was conducted.Nineteen novel lncRNAs that were differentially expressed(DE)only in the NIL at 18 days after flowering(i.e.,α-null-associated DE lncRNAs)were delected.Sixteen putative soybean stress-responsive lncRNAs were identified,and observed to regulate 257 stress-related genes DE in the NIL.This result indicated that theα-null allele might represent an intrinsic defect stress that altered the expression of various stress-related genes inα-null-type hypoallergenic soybean.Additionally,25 epigenetic-related lncRNAs regulated 831 DE epigenetic-related genes and simultaneously initiated multiple epigenetic activities,including ubiquitination,methylation and acetylation.Kyoto encyclopedia of genes and genomes(KEGG)analysis indicated that the biosynthesis of amino acids pathway was enriched with 83 DE genes regulated by nine DE lncRNAs.Changes in the expression of these lncRNAs and genes might be the reason for the altered amino acid composition in the NIL.Among all detected DE lncRNAs,MSTRG.12518 was the most conspicuousα-null-specific cis/trans-lnc RNA that played an efficient,versatile and vital role in the NIL.The data indicated that the lnc RNA profile differed between the NIL and DN47.Variations in lncRNAs,gene expression levels and DNA methylation states likely contributed to the intrinsic defect stress response mechanism inα-null-type hypoallergenic soybeans.
基金supported by the National Natural Science Foundation of China(82003228)the Natural Science Foundation of Jiangsu Province(BK20201080)the Research Project of Clinical Medical Science and Technology Development Fund of Jiangsu University(JLY2021097).
文摘Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and neck squamous cell carcinoma(HNSCC).RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas.In the training group,we used Pearson correlation,univariate Cox regression,least absolute shrinkage/selection operator regression analyses,and multivariate Cox regression to build a prognostic model.In the test group,we evaluated the model.Multivariate Cox regression was done to screen out independent prognostic factors,with which we constructed a nomogram.Afterward,we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics.Gene set enrichment analysis,immune correlation analysis,and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.The most important LINC00861 in the model was examined in HNE1,CNE1,and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid.In addition,CCK-8,Edu,and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells.The signature based on nine ARLs has a good predictive value in survival time,immune infiltration,immune checkpoint expression,and sensitivity to multiple drugs.LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells,and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines.This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC.LINC00861 is a protective factor for the development of HNSCC.
