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.

Curcumin inhibits the growth and invasion of gastric cancer by regulating long noncoding RNA AC022424.2

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.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p

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.

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.

Integrating disulfidptosis-related long noncoding RNAs in colorectal cancer prognosis:A path to precision medicine

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.

Role of noncoding RNAs in liver fibrosis

Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.

Prognostic value of the long noncoding RNA AFAP1-AS1 in cancers

Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Methods PubMed,EMBASE,and Cochrane Library were systematically searched.Hazard ratios(HRs)with 95%confidence intervals(CIs)were used to assess the prognostic value based on overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS).Odds ratios(ORs)with 95%CIs were used to determine the relationships between AFAP1-AS1 and clinicopathological features,such as large tumor size(LTS),high tumor stage(HTS),poor histological grade(PHG),lymph node metastasis(LNM),and distant metastasis(DM).Results Thirty-five eligible articles and 3433 cases were analyzed.High AFAP1-AS1 expression,compared to low AFAP1-AS1 expression,correlated with significantly shorter OS(HR=2.15,95%CI=1.97-2.34,P<0.001),DFS(HR=1.37,95%CI=1.19-1.57,P<0.001),and PFS(HR=1.97,95%CI=1.56-2.50,P<0.001)in patients with cancer.In various cancers,elevated AFAP1-AS1 expression was significantly associated with LTS(OR=2.76,95%CI=2.16-3.53,P<0.001),HTS(OR=2.23,95%CI=1.83-2.71,P<0.001),and PHG(OR=1.39,95%CI=1.08-1.79,P=0.01)but not LNM(OR=1.59,95%CI=0.88-2.85,P=0.12)or DM(OR=1.81,95%CI=0.90-3.66,P=0.10).Conclusion High AFAP1-AS1 expression was associated with prognostic and clinicopathological features,suggesting that AFAP1-AS1 is a prognostic biomarker for human cancers.

Molecular mechanisms of noncoding RNA and epigenetic regulation in obesity with consequent diabetes mellitus development

Diabetes mellitus(DM)and obesity have become two of the most prevalent and challenging diseases worldwide,with increasing incidence and serious complications.Recent studies have shown that noncoding RNA(ncRNA)and epigenetic regulation play crucial roles in the pathogenesis of DM complicated by obesity.Identification of the involvement of ncRNA and epigenetic regulation in the pathogenesis of diabetes with obesity has opened new avenues of investigation.Targeting these mechanisms with small molecules or RNA-based therapies may provide a more precise and effective approach to diabetes treatment than traditional therapies.In this review,we discuss the molecular mechanisms of ncRNA and epigenetic regulation and their potential therapeutic targets,and the research prospects for DM complicated with obesity.

Novel insights regarding the role of noncoding RNAs in diabetes

Diabetes mellitus(DM)is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance,inadequate insulin secretion,or excessive glucagon secretion.In 2021,the global prevalence of diabetes is anticipated to be 10.7%(537 million people).Noncoding RNAs(ncRNAs)appear to have an important role in the initiation and progression of DM,according to a growing body of research.The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs.miRNAs are singlestranded,short(17–25 nucleotides),ncRNAs that influence gene expression at the post-transcriptional level.Because DM has reached epidemic proportions worldwide,it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently.miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation.In this review,we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory miRNAs involved in these disorders.We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM.We examine and synthesize recent research that used novel,high-throughput technologies to uncover ncRNAs involved in DM,necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses.

Identification and characterization of noncoding RNAs-associated competing endogenous RNA networks in major depressive disorder

BACKGROUND Major depressive disorder(MDD)is a common and serious mental illness.Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing.Recently,noncoding RNAs(ncRNAs)were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence;however,the interplay among RNA species,including protein-coding RNAs and ncRNAs,in MDD remains unclear.AIM To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA(lncRNAs),microRNAs(miRNAs),and mRNAs between MDD and controls.METHODS Gene expression data were searched in NCBI Gene Expression Omnibus using the search term“major depressive disorder.”Six array datasets from humans were related to the search term:GSE19738,GSE32280,GSE38206,GSE52790,GSE76826,and GSE81152.These datasets were processed for initial assessment and subjected to quality control and differential expression analysis.Differentially expressed lncRNAs,miRNAs,and mRNAs were determined,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed,and protein-protein interaction network was generated.The results were analyzed for their association with MDD.RESULTS After analysis,3 miRNAs,12 lncRNAs,and 33 mRNAs were identified in the competing endogenous RNA network.Two of these miRNAs were earlier shown to be involved in psychiatric disorders,and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The expression of hub gene fatty acid 2-hydroxylase was enriched,and the encoded protein was found to be involved in myelin formation,indicating that neurological development and signal transduction are involved in MDD pathogenesis.CONCLUSION The present study presents candidate nc RNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.

Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly understood.AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.METHODS We measured the expression of lncRNA W42 in HCC tissues and cells(Huh7 and SMMC-7721)by quantitative reverse transcriptase polymerase chain reaction.Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression.HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42.Cell functions were detected by cell counting Kit-8(CCK-8),colony formation,flow cytometry and Transwell assays.The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays.An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo.The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.RESULTS In this study,we identified a novel lncRNA(lncRNA W42),and investigated its biological functions and clinical significance in HCC.LncRNA W42 expression was upregulated in HCC tissues and cells.Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC,and inhibited cell apoptosis.LncRNA W42 directly bound to DBN1 and activated the downstream pathway.LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo.The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42,which is upregulated in HCC,may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.

Noncoding RNAs in gastric cancer: Research progress and prospects

Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer(GC). In the past few years, an accumulating body of evidence has deepened our understanding of nc RNAs, and several emerging nc RNAs have been identified, such as PIWI-interacting RNAs(pi RNAs) and circular RNAs(circ RNAs). The competing endogenous RNA(ce RNA) networks include m RNAs, micro RNAs, long nc RNAs(lnc RNAs) and circ RNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of nc RNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ce RNA network in GC.

Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer

AIM To investigate the role of long noncoding RNA(lnc RNA) RP4 in colorectal cancer.METHODS Lentivirus-mediated lnc RNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lnc RNA RP4 mechanism involved assessment of the association of its expression with mi R-7-5 p and the SH3 GLB1 gene. Western blot analysis was also performed to assess the effect of lnc RNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase(PI3 K)/Akt signaling.RESULTS Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lnc RNA RP4. Functional experiments indicated that lnc RNA RP4 directly upregulated SH3 GLB1 expression by acting as a competing endogenous RNA(ce RNA) for mi R-7-5 p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3 K and Akt phosphorylation in colorectal cancer cells in vivo.CONCLUSION Our results demonstrated that lnc RNA RP4 is a ce RNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.

Long noncoding RNAs in hepatitis B virus-related hepatocellular carcinoma

AIM: To study the expression of long noncoding RNAs(lncRNAs) in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).METHODS: The lncRNA profiles between HBV-related HCC tissues and corresponding normal liver tissues were generated using microarray analysis. Datasets were analyzed using multiple algorithms to depict alterations in gene expression on the basis of gene ontology(GO), pathway analysis, and lncRNA levels.RESULTS: The microarray revealed that 1772 lncRNAs and 2508 mRNAs were differently expressed. The pathway analysis demonstrated that the cell cycle, cytokinecytokine receptor interaction, chemokine signaling pathway, and phosphoinositide 3-kinase-protein kinase B signaling pathway may play important roles in HCC.Several GO terms, such as cell cycle, DNA replication,immune response, and signal transduction, were enriched in gene lists, suggesting a potential correlation with HBVrelated HCC. The upregulated large intergenic noncoding RNA ULK4P2 was physically combined with enhancer of zeste homolog 2. Therefore, the lncRNAs may participate in regulating HBV-related HCC.CONCLUSION: lncRNAs play important roles in HCC,future studies should verify whether large intergenic noncoding ULK4P2 functions by combining with enhancer of zeste homolog 2 in HCC.

Overview of noncoding RNAs involved in the osteogenic differentiation of periodontal ligament stem cells

Periodontal diseases are infectious diseases that are characterized by progressive damage to dental support tissue.The major goal of periodontal therapy is to regenerate the periodontium destroyed by periodontal diseases.Human periodontal ligament(PDL)tissue possesses periodontal regenerative properties,and periodontal ligament stem cells(PDLSCs)with the capacity for osteogenic differentiation show strong potential in clinical application for periodontium repair and regeneration.Noncoding RNAs(ncRNAs),which include a substantial portion of poly-A tail mature RNAs,are considered“transcriptional noise.”Recent studies show that ncRNAs play a major role in PDLSC differentiation;therefore,exploring how ncRNAs participate in the osteogenic differentiation of PDLSCs may help to elucidate the underlying mechanism of the osteogenic differentiation of PDLSCs and further shed light on the potential of stem cell transplantation for periodontium regeneration.In this review paper,we discuss the history of PDLSC research and highlight the regulatory mechanism of ncRNAs in the osteogenic differentiation of PDLSCs.

Long noncoding RNA HOXA11-AS promotes gastric cancer cell proliferation and invasion via SRSF1 and functions as a biomarker in gastric cancer

BACKGROUND Gastric cancer (GC) is the fourth most frequent malignancy all over the world. The diagnosis of GC is challenging and the prognosis of GC is very unfavorable. Accumulating evidence reveals that serum long noncoding RNAs (lncRNAs) can function as biomarkers in various types of cancers, including GC. AIM To explore the level and molecular mechanism of the lncRNA HOXA11-AS in GC and the diagnostic and prognostic significance of serum HOXA11-AS in GC. METHODS HOXA11-AS levels in GC tissue, cell lines, and serum samples were measured. The correlation between HOXA11-AS expression and clinicopathological characteristics was analyzed. The role of HOXA11-AS in the diagnosis and prognosis of GC was evaluated. Cell function assays were performed for exploration of the roles of HOXA11-AS in GC cells. Moreover, Western blot was performed to explore the target regulated by HOXA11-AS in GC cells. RESULTS Up-regulation of HOXA11-AS was found in GC tissues, cell lines, and serum samples. In GC patients, decreased serum HOXA11-AS levels were negatively related with tumor size, TNM stage, and lymph node metastasis. The area under the receiver operating characteristic curve of serum HOXA11-AS in the diagnosis of GC was 0.924 (95%CI: 0.881-0.967;sensitivity, 0.787;specificity 0.978). Results of the Kaplan-Meier survival curves suggested the GC patients with a lower HOXA11-AS level having a better overall survival rate. HOXA11-AS promoted GC cell proliferation and invasion. SRSF1 may be the target regulated by HOXA11-AS in GC cells. CONCLUSION HOXA11-AS promotes GC cell proliferation and invasion via SRSF1 and may function as a promising marker in GC.

Diagnostic and therapeutic application of noncoding RNAs for hepatocellular carcinoma

Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miR NAs and lncR NAs in hepatocellular carcinoma(HCC) are frequently observed,clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently e xpe c t e d. H e r e,we s ummar iz e r e c e nt f indings regarding deregulated mi RNAs and lnc RNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically,we emphasize the deregulated expression levels of such noncoding RNAs in patients' sera as noninvasive biomarkers,a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics,we further summarize clinical and preclinical trials using oligonucleotides involving the use of miR NAs and small interfering RNAs against HCC as novel therapeutics. Finally,we discuss current open questions,which must be clarified in the near future for realistic clinical applications of these new strategies.

Exploring prognostic potential of long noncoding RNAs in colorectal cancer based on a competing endogenous RNA network

BACKGROUND Colorectal cancer(CRC)is one of the most prevalent tumors worldwide.Recently,long noncoding RNAs(lncRNAs)have been shown to influence tumorigenesis and tumor progression by acting as competing endogenous RNAs(ceRNAs).It is difficult to extract prognostic lncRNAs and useful bioinformation from most ceRNA networks constructed previously.AIM To construct a prognostic related ceRNA regulatory network and lncRNA related signature based on risk score in CRC.METHODS RNA transcriptome profile and clinical information of 506 CRC patients were downloaded from the Cancer Genome Atlas database.R packages and Perl program were used for data processing.Cox regression analysis was used for prognostic model construction.Quantitative real-time polymerase chain reaction was used to detect the expression of lncRNAs.RESULTS A prognostic-related ceRNA network was constructed,including 9 lncRNAs,44 mRNAs,and 30 miRNAs.In addition,a four-lncRNA model was constructed using multivariate Cox regression analysis,which could be an independent prognostic model in CRC.The risk score for each patient was calculated,and the 506 patients were divided into high and low-risk groups(253 for each group)based on the median risk score.The results of the survival analysis showed that patients with a high-risk score had a poor survival rate.Furthermore,the predictive value of the four-lncRNA model was evaluated in GSE38832.Patient survival probabilities could be better predicted when combing the risk score and clinical features.Gene Set Enrichment Analysis results verified that a number of cancer-related signaling pathways were enriched with a high-risk score in CRC.Finally,we validated a novel lncRNA(LINC00488)using quantitative real-time polymerase chain reaction in 22 paired CRC patient tumor tissues compared to adjacent non-tumor tissues.CONCLUSION The four-lncRNA model could give better predictive value for CRC patients.Our understanding of the lncRNA-related ceRNA regulatory mechanism could provide a potential diagnostic indicator for CRC patients.

Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn's disease

AIM: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn&#x02019;s disease (CD) patients.METHODS: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort.RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and {'type':'entrez-nucleotide','attrs':{'text':'AF113016','term_id':'6642755','term_text':'AF113016'}}AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 ({'type':'entrez-nucleotide','attrs':{'text':'NR_033913','term_id':'299890801','term_text':'NR_033913'}}NR_033913, {'type':'entrez-nucleotide','attrs':{'text':'NR_038218','term_id':'333360887','term_text':'NR_038218'}}NR_038218, {'type':'entrez-nucleotide','attrs':{'text':'NR_036512','term_id':'302393555','term_text':'NR_036512'}}NR_036512, {'type':'entrez-nucleotide','attrs':{'text':'NR_049759','term_id':'388240827','term_text':'NR_049759'}}NR_049759, {'type':'entrez-nucleotide','attrs':{'text':'NR_033951','term_id':'300068996','term_text':'NR_033951'}}NR_033951, {'type':'entrez-nucleotide','attrs':{'text':'NR_045408','term_id':'354548835','term_text':'NR_045408'}}NR_045408, {'type':'entrez-nucleotide','attrs':{'text':'NR_038377','term_id':'335334999','term_text':'NR_038377'}}NR_038377 and {'type':'entrez-nucleotide','attrs':{'text':'NR_039976','term_id':'337756399','term_text':'NR_039976'}}NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network.CONCLUSION: The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration.