Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study

BACKGROUND Our previous study reported that the single-nucleotide polymorphism(SNP)rs155979 GC in the promoter region of long-chain non-coding RNA(lncRNA)NONHSAT102891 affects depression susceptibility in a Chinese population.AIM To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population.METHODS This this case-control association study was approved by the Ethics Committee of Chengdu Medical College(approval number:201815).Patient diagnosis was based on DSM-IV criteria.We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology,and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects.The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells.RESULTS Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times[TC/CC vs TT:odds ratio(OR)=1.59,95%confidence interval(CI):1.08-2.35,P=0.019].The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230,and the double SNP CG haplotype was more common in the control group compared to case group,indicating that this haplotype significantly reduced the risk of depression(C/G vs T/A:OR=0.42,95%CI:0.21-0.83,P=0.01).There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group(P>0.05),indicating that the double SNP haplotype has no transcrip-tional activity.CONCLUSION The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

Cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma

BACKGROUND Cuproptosis has recently been considered a novel form of programmed cell death.To date,long-chain non-coding RNAs(lncRNAs)crucial to the regulation of this process remain unelucidated.AIM To identify lncRNAs linked to cuproptosis in order to estimate patients'prognoses for hepatocellular carcinoma(HCC).METHODS Using RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma(TCGA-LIHC),a co-expression network of cuproptosis-related genes and lncRNAs was constructed.For HCC prognosis,we developed a cuproptosisrelated lncRNA signature(CupRLSig)using univariate Cox,lasso,and multivariate Cox regression analyses.Kaplan-Meier analysis was used to compare overall survival among high-and low-risk groups stratified by median CupRLSig risk score.Furthermore,comparisons of functional annotation,immune infiltration,somatic mutation,tumor mutation burden(TMB),and pharmacologic options were made between high-and low-risk groups.RESULTS Three hundred and forty-three patients with complete follow-up data were recruited in the analysis.Pearson correlation analysis identified 157 cuproptosis-related lncRNAs related to 14 cuproptosis genes.Next,we divided the TCGA-LIHC sample into a training set and a validation set.In univariate Cox regression analysis,27 LncRNAs with prognostic value were identified in the training set.After lasso regression,the multivariate Cox regression model determined the identified risk equation as follows:Risk score=(0.2659×PICSAR expression)+(0.4374×FOXD2-AS1 expression)+(-0.3467×AP001065.1 expression).The CupRLSig high-risk group was associated with poor overall survival(hazard ratio=1.162,95%CI=1.063-1.270;P<0.001)after the patients were divided into two groups depending upon their median risk score.Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as the validation set.The area under the curve of 0.741 was found to be a better predictor of HCC prognosis as compared to other clinicopathological variables.Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses(median survival of 30 mo vs 102 mo of low-risk combinations with low TMB group).The low-risk group had more activated natural killer cells(NK cells,P=0.032 by Wilcoxon rank sum test)and fewer regulatory T cells(Tregs,P=0.021)infiltration than the high-risk group.This finding could explain why the low-risk group has a better prognosis.Interestingly,when checkpoint gene expression(CD276,CTLA-4,and PDCD-1)and tumor immune dysfunction and rejection(TIDE)scores are considered,highrisk patients may respond better to immunotherapy.Finally,most drugs commonly used in preclinical and clinical systemic therapy for HCC,such as 5-fluorouracil,gemcitabine,paclitaxel,imatinib,sunitinib,rapamycin,and XL-184(cabozantinib),were found to be more efficacious in the low-risk group;erlotinib,an exception,was more efficacious in the high-risk group.CONCLUSION The lncRNA signature,CupRLSig,constructed in this study is valuable in prognostic estimation of HCC.Importantly,CupRLSig also predicts the level of immune infiltration and potential efficacy of tumor immunotherapy.