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.

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.

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.

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.

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.

Long noncoding RNAs in neurodevelopment and Parkinson’s disease

Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.

Noncoding RNAs as additional mediators of epigenetic regulation innonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common causeof chronic liver disorder worldwide. It represents a spectrum that includes acontinuum of different clinical entities ranging from simple steatosis to nonalcoholicsteatohepatitis, which can evolve to cirrhosis and in some cases tohepatocellular carcinoma, ultimately leading to liver failure. The pathogenesis ofNAFLD and the mechanisms underlying its progression to more pathologicalstages are not completely understood. Besides genetic factors, evidence indicatesthat epigenetic mechanisms occurring in response to environmental stimuli alsocontribute to the disease risk. Noncoding RNAs (ncRNAs), including microRNAs,long noncoding RNAs, and circular RNAs, are one of the epigenetic factors thatplay key regulatory roles in the development of NAFLD. As the field of ncRNAsis rapidly evolving, the present review aims to explore the current state ofknowledge on the roles of these RNA species in the pathogenesis of NAFLD,highlight relevant mechanisms by which some ncRNAs can modulate regulatorynetworks implicated in NAFLD, and discuss key challenges and future directionsfacing current research in the hopes of developing ncRNAs as next-generationnon-invasive diagnostics and therapies in NAFLD and subsequent progression tohepatocellular carcinoma.

Long noncoding RNAs in gastric cancer: From molecular dissection to clinical application

Long noncoding RNAs(lncRNAs)are important regulators of cell processes that are usually dysregulated in gastric cancer(GC).Based on their high specificity and ease of detection in tissues and body fluids,increasing attention has spurred the study of the roles of lncRNAs in GC patients.Thus,it is necessary to elucidate the molecular mechanisms and further explore the clinical applications of lncRNAs in GC.In this review,we summarize current knowledge to examine dysregulated lncRNAs in GC and their underlying molecular mechanisms and activities in GC,which involve microRNA sponging,mRNA stability,genetic variants,alternative splicing,transcription factor binding,and epigenetic modification.More significantly,the potential of lncRNAs as prognostic,circulating,and drug-resistant biomarkers for GC is also described.This review highlights the method of dissecting molecular mechanisms to explore the clinical application of lncRNAs in GC.Overall,this review offers assistance in using lncRNAs as novel candidates for molecular mechanisms and for the identification of revolutionary biomarkers for GC.

Metastasis-associated long noncoding RNAs in gastrointestinal cancer: Implications for novel biomarkers and therapeutic targets

Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lnc RNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lnc RNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lnc RNAs, and evaluate the p o t e n t i a l r o l e s o f l n c R N A s a s n o v e l d i a g n o s t i c biomarkers and therapeutic targets in gastrointestinal cancer.

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering.The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.

Noncoding RNAs as drivers of the phenotypic plasticity of oesophageal mucosa

The histological commitment of the lower oesophageal mucosa largely depends on a complex molecular landscape. After extended inflammatory insult due to gastroesophageal reflux disease,squamous oesophageal mucosa may differentiate into columnar metaplastic mucosa. In this setting,the presence of intestinal metaplasia is considered the starting point of Barrett's carcinogenetic cascade. Aside from secondary prevention strategies for Barrett's mucosa(BM) patients,there are multiple endoscopic ablative therapies available for BM eradication and for the replacement of metaplastic epithelia with a neosquamous mucosa. However,BM frequently recurs in a few years,which supports the notable phenotypic plasticity of the oesophageal mucosa. In recent years,several reports pinpointed a class of small noncoding RNAs,the micro RNAs(mi RNAs),as principal effectors and regulators of oesophageal mucosa metaplastic(and neoplastic) transformation. Because of mi RNAs notable stability in fixed archival diagnostic specimens,expression profiling of mi RNAs represent an innovative diagnostic,prognostic and predictive tool in the stratification of phenotypic alterations in the oesophageal mucosa.

Long noncoding RNAs in hepatitis B virus replication and oncogenesis

Several diverse long noncoding RNAs(lncRNAs)have been identified to be involved in hepatitis B virus(HBV)replication and oncogenesis,especially those dysregulated in HBV-related hepatocellular carcinoma(HCC).Most of these dysregulated lncRNAs are modulated by the HBV X protein.The regulatory mechanisms of some lncRNAs in HBV replication and oncogenesis have been characterized.Genetic polymorphisms of several lncRNAs affecting HBV replication or oncogenesis have also been studied.The prognosis of HCC remains poor.It is important to identify novel tumor markers for early diagnosis and find more therapeutic targets for effective treatments of HCC.Some dysregulated lncRNAs in HBV-related HCC may become biomarkers for early diagnosis and/or the therapeutic targets of HCC.This mini-review summarizes these findings briefly,focusing on recent developments.

Identification of key long noncoding RNAs and their biological functions in hepatocellular carcinoma

Long noncoding RNAs(lncRNAs)are vital regulators in tumorigenesis and metastasis.However,the pathological role of lncRNAs in hepatocellular carcinoma(HCC)is still unclear.In this study,we filtered out three lncRNAs from The Cancer Genome Atlas(TCGA)data that were screened for basic expression and clinical research.We selected lncRNA-NEAT1 for further study to explore its function in HCC progression and its regulatory mechanism.We identified three differentially expressed lncRNAs(DElncRNAs)in tumor and adjacent normal tissues from the TCGA library using data mining methods:lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11.Their basic expression levels were detected by qPCR.Then,we selected lncRNA-NEAT1 as a potentially important lncRNA to verity its biological function and mechanism in HCC cell lines.lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11 were overexpressed in liver cancer tissues and cell lines.We found that silencing NEAT1 in vitro can inhibit the proliferation of HuH-7 and Li-7 cells,inhibit cell migration,and induce apoptosis as well as significantly increase the level of miR-16-5p.We also confirmed that miR-16-5p has a significant correlation with Bcl-2.When NEAT1 is silenced,the expression of Bcl-2 decreases.Inhibiting miR-16-5p can restore Bcl-2 to its original level.We conclude that miR-16-5p1/lncRNA NEAT1 plays a crucial role in regulating the delivery of Bcl-2 in HCC.Overall,the miR-16-5p/lncRNA-NEAT1/Bcl-2 signaling axis may be a promising target for HCC treatment.

Genome-wide identification and prediction of long noncoding RNAs in half-smooth tongue sole Cynoglossus semilaevis

At present,the function and profile of long noncoding RNAs(lncRNAs)in half-smooth tongue soles Cynoglossus semilaevis remain poorly understood.Therefore,we identified lncRNAs in the species using large-scale deep sequencing approaches.A total of 96726222 clean reads and 2497 lncRNAs were obtained from the compound samples.In total,1694 known lncRNAs and 803 novel lncRNAs were identified.Most of the novel lncRNAs distributed mainly in a range of 200-3000 nt and contained 2-6 exons.Six novel lncRNAs were selected for expression analysis by quantitative reverse transcription-polymerase chain reaction,of which lnc_770 and lnc_150 were expressed mainly in the ovary.This study provides a valuable resource for lncRNA studies of half-smooth tongue sole and improves our understanding of the function of non-coding RNA in fish.

Long noncoding RNAs in mesenchymal stromal/stem cells osteogenic differentiation:Implications in osteoarthritis pathogenesis

This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it discusses a novel modality of epigenetic regulation,the long noncoding RNAs(lncRNAs),and provides evidence of their involvement in mesenchymal stromal/stem cells osteo-/adipogenic differentiation balance.Despite focus on lncRNAs,there is an emerging cross talk between lncRNAs and miRNAs interaction as a novel mechanism in the regulation of the function of the musculoskeletal system,by controlling bone homeostasis and bone regeneration,as well as the osteogenic differentiation of stem cells.Thus,we touched on some examples to demonstrate this interaction.In addition,we believe there is still much to discover from the effects of lncRNAs on progenitor and non-progenitor cell differentiation.We incorporated data from other published articles to review lncRNAs in normal progenitor cell osteogenic differentiation,determined lncRNAs involved in osteoarthritis pathogenesis in progenitor cells,and provided a review of lncRNAs in non-progenitor cells that are differentially regulated in osteoarthritis.In conclusion,we really enjoyed reading this article and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.

Exosomal noncoding RNAs in cholangiocarcinoma:Laboratory noise or hope?

Currently,extracellular vesicles and particularly exosomes have gained a lot of research interest due to their unique roles in several biological processes.Noncoding RNAs(microRNAs,long noncoding RNAs and circular RNAs)represent a class of functional RNA with distinct regulatory roles in tumorigenesis and cancer progression.Cholangiocarcinoma is a rare but highly aggressive type of malignancy that is very challenging to diagnose,especially in early stages;surgical resection still represents the sole potentially curative treatment option.Hence,there is an urgent need for the discovery of novel diagnostic and prognostic biomarkers.Hereby,we provide a comprehensive review of the most recent discoveries that focus on exosomal noncoding RNAs in cholangiocarcinoma with the aim to identify new molecular players that could be used as biomarkers and therapeutic targets.

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.

Expression profiles of long noncoding RNAs in retinopathy of prematurity

Long noncoding RNA(lncRNA)regulates the proliferation and migration of human retinal endothelial cells,as well as retinal neovascularization in diabetic retinopathy.Based on similarities between the pathogenesis of retinopathy of prematurity(ROP)and diabetic retinopathy,lncRNA may also play a role in ROP.Seven-day-old mice were administered 75±2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP model.Expression of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology,and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The results showed that compared with the control group,57 lncRNAs were differentially expressed,including 43 upregulated and 14 downregulated,in the retinal tissue of ROP mice.Compared with control mice,42 mRNAs were differentially expressed in the retinal tissue of ROP mice,including 24 upregulated and 18 downregulated mRNAs.Differentially expressed genes were involved in ocular development and related metabolic pathways.The differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling pathways.Our results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP treatment.This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25,2016(approval No.2016PS074K).

Long noncoding RNAs:new insights in modulating mammalian spermatogenesis

Spermatogenesis is a complex differentiating developmental process in which undifferentiated spermatogonial germ cells differentiate into spermatocytes,spermatids,and finally,to mature spermatozoa.This multistage developmental process of spermatogenesis involves the expression of many male germ cell-specific long noncoding RNAs(lncRNAs)and highly regulated and specific gene expression.LncRNAs are a recently discovered large class of noncoding cellular transcripts that are still relatively unexplored.Only a few of them have postmeiotic;however,lncRNAs are involved in many cellular biological processes.The expression of lncRNAs is biologically relevant in the highly dynamic and complex program of spermatogenesis and has become a research focus in recent genome studies.This review considers the important roles and novel regulatory functions whereby lncRNAs modulate mammalian spermatogenesis.