Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis

Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

Clinical application value of long non-coding RNAs signatures of genomic instability in predicting prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)presents challenges due to its high recurrence and metastasis rates and poor prognosis.While current clinical diagnostic and prognostic indicators exist,their accuracy remains imperfect due to their biol-ogical complexity.Therefore,there is a quest to identify improved biomarkers for HCC diagnosis and prognosis.By combining long non-coding RNA(lncRNA)expression and somatic mutations,Duan et al identified five representative lncRNAs from 88 lncRNAs related to genomic instability(GI),forming a GI-derived lncRNA signature(LncSig).This signature outperforms previously re-ported LncSig and TP53 mutations in predicting HCC prognosis.In this editorial,we comprehensively evaluate the clinical application value of such prognostic evaluation model based on sequencing technology in terms of cost,time,and practicability.Additionally,we provide an overview of various prognostic models for HCC,aiding in a comprehensive understanding of research progress in pro-gnostic evaluation methods.

Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

Urgent need for prognostic markers for hepatocellular carcinoma in the light of genomic instability and non-coding RNA signatures

In this editorial,we comment on an original article by Duan et al.Despite ad-vancements in the diagnosis and treatment of hepatocellular carcinoma(HCC),the identification of suitable prognostic factors remains challenging.In their paper,Duan et al identified long non-coding RNAs(LncRNAs)to quantify ge-nomic instability(GI)by combining LncRNA expression and somatic mutation profiles.They confirmed that the GI-derived LncRNA signature(GI-LncSig)could be an independent prognostic factor with the area under the curve of 0.773.Fur-thermore,the authors stated that GI-LncSig may have a better predictive perfor-mance than TP53 mutation status alone.However,studies exploring genetic markers for predicting the prognosis of HCC are crucial for identifying thera-peutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of liver cancer.

Construction and validation of somatic mutation-derived long noncoding RNAs signatures of genomic instability to predict prognosis of hepatocellular carcinoma

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.

Lipid metabolism-related long noncoding RNAs:A potential prognostic biomarker for hepatocellular carcinoma

The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs(lncRNAs)and lipid metabolism play crucial roles in the development and progression of HCC.Enhanced lipid synthesis promotes HCC progression,and lncRNAs can reprogram the expression of lipogenic enzymes.Consequently,lipid metabolism-related(LMR)-lncRNAs regulate lipid anabolism,accelerating the onset and progression of HCC.This suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

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.

New challenges in hepatocellular carcinoma:A role for PIWIinteracting RNAs?

Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development and progression of HCC is central to improving our clinical approaches.PIWIinteracting RNAs(piRNAs)are a class of small non-coding RNAs that bind to PIWI family proteins to regulate gene expression at transcriptional and posttranscriptional levels.A growing body of work shows that the dysregulation of piRNAs plays a crucial role in the progression of various human cancers.In this editorial,we report on the current knowledge of HCC-associated piRNAs and their potential clinical utility.Based on the editorial by Papadopoulos and Trifylli,on the role and clinical evaluation of exosomal circular RNAs in HCC,we highlight this other emerging class of non-coding RNAs.

MicroRNA-206 as a promising epigenetic approach to modulate tumor-associated macrophages in hepatocellular carcinoma

This letter comments on the recently published manuscript by Huang et al in the World Journal of Gastroenterology,which focused on the immunomodulatory effect of Calculus bovis on hepatocellular carcinoma(HCC)tumor microenvironments(TME)by inhibiting M2-tumor-associated macrophage(M2-TAM)polarization via Wnt/β-catenin pathway modulation.Recent research highlights the crucial role of TAMs and their polarization towards the M2 phenotype in promoting HCC progression.Epigenetic regulation,particularly through microRNAs(miR),has emerged as a key factor in modulating immune responses and TAM polarization in the TME,influencing treatment responses and tumor progression.This editorial focuses on miR-206,which has been found to inhibit HCC cell proliferation and migration and promote apoptosis.Moreover,miR-206 enhances anti-tumor immune responses by promoting M1-polarization of Kupffer cells,facilitating CD8+T cell recruitment and suppressing liver cancer stem cell expansion.However,challenges remain in understanding the precise mechanisms regulating miR-206 and its potential as a therapeutic agent.Targeting epigenetic mechanisms and improving strategies,whether through pharmacological or genetic approaches,offer promising avenues to sensitize tumor cells to chemotherapy.Understanding the intricate interactions between cancer and non-coding RNA regulation opens new avenues for developing targeted therapies,potentially improving HCC prognosis.

Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification.CONCLUSION We have constructed a six-lncRNA signature for prognosis prediction of HCC.This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion

BACKGROUND Highly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) which has recently been identified as a key regulator in hepatocellular carcinoma (HCC) progression. However, its role in the secretion of exosomes from HCC cells remains unknown. AIM To explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells. METHODS Serum and liver tissue samples were collected from 30 patients with HCC who had not received chemotherapy, radiotherapy, or immunotherapy before surgery. HULC expression in serum exosomes and liver cancer tissues of patients was measured, and compared with the data obtained from healthy controls and tumor adjacent tissues. The effect of HULC upregulation in HCC cell lines and the relationship between HULC and other RNAs were studied using qPCR and dualluciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.RESULTS HULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in tumor adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis (TNM) classification, and HULC expression in tissues correlated with that in serum exosomes. Upregulation of HULC promoted HCC cell growth and invasion and repressed apoptosis. Notably, it also facilitated the secretion of exosomes from HCC cells. Moreover, qPCR assays showed that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggested that miR-372-3p could directly bind both HULC and Rab11a. CONCLUSION Our findings illustrate the importance of the HULC/miR-372-3p/Rab11a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells.

Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma

AIM To construct a long non-coding RNA(lnc RNA) signature for predicting hepatocellular carcinoma(HCC) prognosis with high efficiency.METHODS Differentially expressed lnc RNAs(DELs) between HCC specimens and peritumor liver specimens were identified using the edge R package to analyze The Cancer Genome Atlas(TCGA) LIHC dataset.Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival(OS) in a training set.These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model.Those lnc RNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula.The prognostic value ofthis formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lnc RNAs in the signature.RESULTS Based on lnc RNA expression profiling of 370 HCC patients from the TCGA database,we constructed a 5-lnc RNA signature(AC015908.3,AC091057.3,TMCC1-AS1,DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis.HCC patients with high-risk scores based on the expression of the 5 lnc RNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups.Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lnc RNAs was independent of clinicopathological parameters.A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lnc RNA signature showed improved prognostic power compared with the other two signatures.Functional enrichment analysis indicated that the 5 lnc RNAs were potentially involved in metabolic processes,fibrinolysis and complement activation.CONCLUSION Our present study constructed a 5-lnc RNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.

Advancing prognostic understanding in hepatocellular carcinoma through the integration of genomic instability and lncRNA signatures: GILncSig model

The recently published study by Duan et al introduces a promising method that combines genomic instability and long non-coding RNAs to improve the prognostic evaluation of hepatocellular carcinoma(HCC),a deadly cancer associated with considerable morbidity and mortality.This editorial aims to analyze the methodology,key findings,and broader implications of the study within the fields of gastroenterology and oncological surgery,highlighting the shift towards precision medicine in the management of HCC.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

Expression Profile of Altered Long Non-coding RNAs in Patients with HBV-associated Hepatocellular Carcinoma

In China, hepatitis B virus （HBV） infection is the major cause of hepatocellular carcinoma （HCC）, which is called HBV-related HCC （HBV-HCC）, but the pathogenesis has not been clearly elu- cidated. Long non-coding RNAs （lncRNAs） have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially ex- pressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by mi- croarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function （gene ontology, pathway analysis） of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 （4.30%） lncRNAs exhibited more than two-fold change （P〈0.05）; 325 were up-regulated, and 512 were down-regulated; 991 （5.70%） mRNAs exhibited more than 2-fold change （P〈0.05）; 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 （53.05%） lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important bio- logical regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase （MAPK） signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues （P〈0.05）. It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carci- noma-related signaling pathway and MAPK signaling pathways.

Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets

BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the potential prognostic factors for HCC.However,the role of combined application of lncRNAs in estimating overall survival(OS)for hepatitis virus positive HCC(VHCC)is uncertain.AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODS The expression patterns of lncRNAs,as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database.The R package was adopted to obtain the differentially expressed lncRNAs(DElncRNAs).LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis,so as to construct a least absolute shrinkage and selection operator(LASSO)model.Subsequently,the constructed lncRNA signature was developed and validated.Afterwards,the prognostic nomogram was established,which combined the as-established lncRNA signature as well as the clinical features.Meanwhile,subgroup analysis stratified by the virus type was also performed.Finally,the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly coexpressed genes.RESULTS A total of 1420 DElncRNAs were identified,among which 406 were significant in univariate Cox regression analysis.LASSO regression confirmed 8 out of the 406 lncRNAs,including AC005722.2,AC107959.3,AL353803.1,AL589182.1,AP000844.2,AP002478.1,FLJ36000,and NPSR1-AS1.Then,the prognostic risk score was calculated.Our results displayed a significant association between the risk model and the OS of VHCC[hazard ratio=1.94,95%confidence interval(CI):1.61-2.34,log-rank P=2e-10].The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC.Furthermore,a nomogram was plotted,and the concordance index of internal validation was 0.763(95%CI:0.700-0.826).Moreover,the subgroup analysis regarding etiology confirmed this risk model.In addition,the Wnt signaling pathway,angiogenesis,the p53 pathway,and the PI3 kinase pathway were the remarkably enriched pathways.CONCLUSION An eight-lncRNA signature has been established to predict the prognosis for VHCC,which contributes to providing a novel foundation for the targeted therapy of VHCC.

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications

Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma(HCC). Certain lnc RNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lnc RNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lnc RNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.

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.

The expression and clinical significance of long non-coding RNA LOC728040 in hepatocellular carcinoma

Objective:This study aimed to investigate the expression of long non-coding RNA LOC728040in hepatocellular carcinoma(HCC)tissues and normal tissues.Methods:Quantitative reverse-transcription PCR(qPCR)was performed to detect the expression of LOC728040in HCC tissues and paracancer tissues to explore the differences of the clinical indicators of HCC between two groups of low and high expression.And the target genes prediction of LOC728040as a supplement.Results:The lower expression of LOC728040was found in HCC tissues compared with the paracancer tissues(P<0.05).According to the expression,Patients were divided into two groups,and their occupation,tumor capsular and serum alkaline phosphatase(ALP)were significantly different(P<0.05).We found LOC728040upstream existed an alpha albumin gene(AFM)through the Cis analysis by Blast software.Conclusion:Long non-coding RNA LOC728040was markedly downregulated in HCC tissues and was correlated with occupation tumor capsular and serum ALP.The LOC728040might be a biomarker for detection of HCC or other cancers,but its underlying mechanisms still need further study.

Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma:Dysregulation and implications for early detection,diagnosis and therapy

Hepatitis C virus(HCV)infection is one of main causes of hepatocellular carcinoma(HCC)and the prevalence of HCV-associated HCC is on the rise worldwide.It is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C,and to identify target molecules for the prevention and treatment of HCV-associated-HCC.Small noncoding RNAs,mainly microRNAs(miRNAs),and long non-coding RNAs(lncRNAs)with size greater than 200nucleotides,are likely to play important roles in a variety of biological processes,including development and progression of HCC.For the most part their underlying mechanisms of action remain largely unknown.In recent years,with the advance of high-resolution of microarray and application of next generation sequencing techniques,a significant number of non-coding RNAs(ncRNAs)associated with HCC,particularly caused by HCV infection,have been found to be differentially expressed and to be involved in pathogenesis of HCVassociated HCC.In this review,we focus on recent studies of ncRNAs,especially miRNAs and lncRNAs related to HCV-induced HCC.We summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection,diagnosis and therapy of HCV-associated HCC.We also discuss the limitations of recent studies,and suggest future directions for research in the field.miRNAs,lncRNAs and their target genes may represent new candidate molecules for the prevention,diagnosis and treatment of HCC in patients with HCV infection.Studies of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.