Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Molecular mechanisms underlying roles of long non-coding RNA small nucleolar RNA host gene 16 in digestive system cancers

This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors.The first study,by Zhao et al,explored how hBD-1 affects colon cancer,via the lncRNA TCONS_00014506,by inhibiting mTOR and promoting autophagy.The second one,by Li et al,identified the lncRNA prion protein testis specific(PRNT)as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance,suggesting PRNT as a potential therapeutic target for colorectal cancer.Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers.As a recent research hotspot,SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers.The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA,interacting with other proteins,regulating various genes,and affecting downstream target molecules.This review systematically examines the recently reported biological functions,related molecular mechanisms,and potential clinical significance of SNHG16 in various digestive system cancers,and explores the relationship between SNHG16 and digestive system cancers.The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.

Long non-coding RNAs with essential roles in neurodegenerative disorders

Recently,with the advent of high-resolution and high-throughput sequencing technologies,an increasing number of long non-coding RNAs(lncRNAs)have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns,across different neurodegenerative diseases.However,the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood.This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles,regulatory mechanisms,and research status of lncRNAs in Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis.Finally,this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases,hoping to provide broader implications for developing effective treatments.

Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis

Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.

Emerging roles of non-coding RNAs in gastric cancer:Pathogenesis and clinical implications

Gastric cancer is a leading cause of cancer-related deaths. However, the mechanisms underlying gastric carcinogenesis remain largely unclear. The association of non-coding RNAs(nc RNAs) with cancer has been widely studied during the past decade. In general, nc RNAs have been classified as small nc RNAs, including micro RNAs(mi RNAs), and long non-coding RNAs(lnc RNAs). Emerging evidence shows that mi RNAs and lnc RNAs play key roles in the formation and progression of many cancers. In this review, we focus on the regulation of mi RNAs and lnc RNAs in gastric cancer. mi RNAs and lnc RNAs appear to be involved in gastric tumor growth, invasion, and metastasis and in establishment of the gastric tumor microenvironment through various mechanisms. Furthermore, we also discuss the possibilities of establishing mi RNAs and lnc RNAs as potential biomarkers and therapeutic targets for gastric cancer. Taken together, we summarize the emerging roles of nc RNAs in gastric cancer development and their possible clinical significance.

New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors, epigenetic modifications and non-coding RNAs

Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.

Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction:regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications

Ischemic stroke occurs under a variety of clinical conditions and has different pathogeneses,resulting in necrosis of brain parenchyma.Stroke pathogenesis is characterized by neuroinflammation and endothelial dysfunction.Some of the main processes triggered in the early stages of ischemic damage are the rapid activation of resident inflammatory cells(microglia,astrocytes and endothelial cells),inflammatory cytokines,and translocation of intercellular nuclear factors.Inflammation in stroke includes all the processes mentioned above,and it consists of either protective or detrimental effects concerning the“polarization”of these processes.This polarization comes out from the interaction of all the molecular pathways that regulate genome expression:the epigenetic factors.In recent years,new regulation mechanisms have been cleared,and these include non-coding RNAs,adenosine receptors,and the activity of mesenchymal stem/stromal cells and microglia.We reviewed how long non-coding RNA and microRNA have emerged as an essential mediator of some neurological diseases.We also clarified that their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke.To date,we do not have adequate tools to control pathophysiological processes associated with stroke.Our goal is to review the role of non-coding RNAs and innate immune cells(such as microglia and mesenchymal stem/stromal cells)and the possible therapeutic effects of their modulation in patients with acute ischemic stroke.A better understanding of the mechanisms that influence the“polarization”of the inflammatory response after the acute event seems to be the way to change the natural history of the disease.

Non-coding RNAs as therapeutic targets in cancer and its clinical application

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

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.

Targeting long non-coding RNA MALAT1 alleviates retinal neurodegeneration in diabetic mice

●AIM:To observe the effect of inhibiting long non-coding RNA(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)on diabetic neurodegeneration.●METHODS:Thirty-six 8-week-old C57 BL/6 mice were randomly divided into normal control,diabetic control,diabetic scrambled small interfering RNAs(siRNAs)and diabetic MALAT1-siRNA groups.After diabetic induction with streptozocin intraperitoneally-injection,the diabetic M A L AT 1-s i R N A g ro u p w a s i n t r av i t r e a l l y i n j e c te d with 1μL 20μmol/L MALAT1 siRNA,and the diabetic scrambled siRNA group was injected with the same amount of scrambled siRNA.Electroretinography was performed to examine photoreceptor functions 16 wk after diabetes induction.MALAT1 expression was detected via real time polymerase chain reaction.Cone morphological changes were examined using immunofluorescence.Rod morphological changes were examined by determining outer nuclear layer(ONL)thickness.●RESULTS:The upregulation of retinal MALAT1 expression was detected in the diabetic control mice,while MALAT1 expression in the diabetic MALAT1-siRNA mice was decreased by 91.48%compared to diabetic control mice.The diabetic MALAT1-siRNA and diabetic control mice showed lower a-wave and b-wave amplitudes than did the normal control mice in scotopic and photopic electroretinogram,while the diabetic MALAT1-siRNA mice showed higher amplitudes than diabetic control mice.Morphological examination revealed that ONL thickness in the diabetic MALAT1-siRNA and diabetic control mice was lower than normal control mice.However,ONL thickness was greater in the diabetic MALAT1-siRNA mice than diabetic control mice.Moreover,the diabetic control mice performed a sparser cone cell arrangement and shorter outer segment morphology than diabetic MALAT1-siRNA mice.●CONCLUSION:Inhibiting retinal MALAT1 results in mitigative effects on the retinal photoreceptors,thus alleviating diabetic neurodegeneration.

Tissue-specific differential expression of novel genes and long intergenic non-coding RNAs in humans with extreme response to evoked endotoxemia

Objective Cytokine responses to activation of innate immunity differ between individuals,yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that tissue-specific mRNA and long intergenic non-coding RNA (lincRNA) induction differs between individuals with divergent evoked inflammatory responses.

Navigating the labyrinth of long non-coding RNAs in colorectal cancer:From chemoresistance to autophagy

Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological processes.LncRNA expression can regulate autophagy,which plays dual roles in the initiation and progression of cancers,including CRC.Abnormal expression of lncRNAs is associated with the emergence of chemoresistance.Moreover,it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance.Two recent studies titled“Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506”and“Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription”revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC,respectively.In this editorial,we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical significance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of specific and efficacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as influential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

Discovery and characterization of the first non-coding RNA that regulates gene expression,micF RNA:A historical perspective

The first evidence that RNA can function as a regulator of gene expression came from experiments with prokaryotes in the 1980 s. It was shown that Escherichia coli micF isan independent gene,has its own promoter,and encodes a small non-coding RNA that base pairs with and inhibits translation of a target messenger RNA in response to environmental stress conditions. The mic F RNA was isolated,sequenced and shown to be a primary transcript. In vitro experiments showed binding to the target ompF mR NA. Secondary structure probing revealed an imperfect micF RNA/ompF RNA duplex interaction and the presence of a non-canonical base pair. Several transcription factors,including OmpR,regulate micF transcription in response to environmental factors. micF has also been found in other bacterial species,however,recently Gerhart Wagner and J?rg Vogel showed pleiotropic effects and found micF inhibits expression of multiple target mR NAs; importantly,one is the global regulatory gene lrp. In addition,micF RNA was found to interact with its targets in different ways; it either inhibits ribosome binding or induces degradation of the message. Thus the concept and initial experimental evidence that RNA can regulate gene expression was born with prokaryotes.

Characterization of N6-methyladenosine long non-coding RNAs in sporadic congenital cataract and age-related cataract

AIM:To characterize the N6-methyladenosine(m6A)modification patterns in long non-coding RNAs(lncRNAs)in sporadic congenital cataract(CC)and age-related cataract(ARC).METHODS:Anterior capsule of the lens were collected from patients with CC and ARC.Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs.RESULTS:Large amount of m6A peaks within lncRNA were identified for both CC and ARC,while the level was much higher in ARC(49870 peaks)than that in CC(18688 peaks),yet those difference between ARC in younger age group(ARC-1)and ARC in elder age group(ARC-2)was quite slight.A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs,as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC.On the other hand,5893 hypermethylated and 5213 hypomethylated lncRNAs,as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1.Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles,as well as nucleotide excision repair.CONCLUSION:Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC,providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Long Non-coding RNA ANRIL in Gene Regulation and Its Duality in Atherosclerosis

The antisense transcript long non-coding RNA（lnc RNA）（antisense non-coding RNA in the INK4 locus, ANRIL） is an antisense of the cyclin-dependent kinase inhibitor 2 B（CDKN2B） gene on chromosome 9 p21 that contains an overlapping 299-bp region and shares a bidirectional promoter with alternate open reading frame（ARF）. In the context of gene regulation, ANRIL is responsible for directly recruiting polycomb group（Pc G） proteins, including polycomb repressive complex-1（PRC-1） and polycomb repressive complex-2（PRC-2）, to modify the epigenetic chromatin state and subsequently inhibit gene expression in cis-regulation. On the other hand, previous reports have indicated that ANRIL is capable of binding to a specific site or sequence, including the Alu element, E2 F transcription factor 1（E2F1）, and CCCTC-binding factor（CTCF）, to achieve trans-regulation functions. In addition to its function in cell proliferation, adhesion and apoptosis, ANRIL is very closely associated with atherosclerosis-related diseases. The different transcripts and the SNPs that are related to atherosclerotic vascular diseases（ASVD-SNPs） are inextricably linked to the development and progression of atherosclerosis. Linear transcripts have been shown to be a risk factor for atherosclerosis, whereas circular transcripts are protective against atherosclerosis. Furthermore, ANRIL also acts as a component of the inflammatory pathway involved in the regulation of inflammation, which is considered to be one of the causes of atherosclerosis. Collectively, ANRIL plays an important role in the formation of atherosclerosis, and the artificial modification of ANRIL transcripts should be considered following the development of this disease.

N6-methyladenosine-modified long non-coding RNA KIF9-AS1 promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 expression

BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this therapy.Cancer stem cells play a crucial role in sorafenib resistance in HCC.Our previous study revealed that the long non-coding RNA(lncRNA)KIF9-AS1 is an oncogenic gene in HCC.However,the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear.Herein,we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients.Sphere formation was quantified via a tumor sphere assay.Cell viability,proliferation,and apoptosis were evaluated via Cell Counting Kit-8,flow cytometry,and colony formation assays,respectively.The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation.The tumorigenic role of KIF9-AS1 was validated in a mouse model.RESULTS Compared with that in normal controls,the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues.Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells.Mechanistically,N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1.Additionally,KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination.Furthermore,depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.

Construction of prognostic markers for gastric cancer and comprehensive analysis of pyroptosis-related long non-coding RNAs

BACKGROUND China's most frequent malignancy is gastric cancer(GC),which has a very poor survival rate,and the survival rate for patients with advanced GC is dismal.Pyroptosis has been connected to the genesis and development of cancer.The function of pyroptosis-related long non-coding RNAs(PRLs)in GC,on the other hand,remains uncertain.AIM To explore the construction and comprehensive analysis of the prognostic characteristics of long non-coding RNA(lncRNA)related to pyroptosis in GC patients.METHODS The TCGA database provided us with 352 stomach adenocarcinoma samples,and we obtained 28 pyroptotic genes from the Reactome database.We examined the correlation between lncRNAs and pyroptosis using the Pearson correlation coefficient.Prognosis-related PRLs were identified through univariate Cox analysis.A predictive signature was constructed using stepwise Cox regression analysis,and its reliability and independence were assessed.To facilitate clinical application,a nomogram was created based on this signature.we analyzed differences in immune cell infiltration,immune function,and checkpoints between the high-risk group(HRG)and low-risk group(LRG).RESULTS Five hundred and twenty-three PRLs were screened from all lncRNAs(absolute correlation coefficient>0.4,P<0.05).Nine PRLs were included in the risk prediction signature that was created through stepwise Cox regression analysis.We determined the risk score for GC patients and employed the median value as the dividing line between HRG and LRG.The ability of the risk signature to predict the overall survival(OS)of GC is demonstrated by the Kaplan-Meier analysis,risk curve,receiver operating characteristic curve,and decision curve analysis curve.The risk signature was shown to be an independent prognostic factor for OS in both univariate and multivariate Cox regression analyses.HRG showed a more efficient local immune response or modulation compared to LRG,as indicated by the predicted signal pathway analysis and examination of immune cell infiltration,function,and checkpoints(P<0.05).CONCLUSION In general,we have created a brand-new prognostic signature using PRLs,which may provide ideas for immunotherapy in patients with GC.

Expression and significant roles of the long non-coding RNA CASC19/miR-491-5p/HMGA2 axis in the development of gastric cancer

BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.

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.