Regulatory RNAs,microRNA,long-non coding RNA and circular RNA roles in colorectal cancer stem cells

The properties of cancer stem cells(CSCs),such as self-renewal,drug resistance,and metastasis,have been indicated to be responsible for the poor prognosis of patients with colon cancers.The epigenetic regulatory network plays a crucial role in CSC properties.Regulatory non-coding RNA(ncRNA),including microRNAs,long noncoding RNAs,and circular RNAs,have an important influence on cell physiopathology.They modulate cells by regulating gene expression in different ways.This review discusses the basic characteristics and the physiological functions of colorectal cancer(CRC)stem cells.Elucidation of these ncRNAs will help us understand the pathological mechanism of CRC progression,and they could become a new target for cancer treatment.

Regulatory RNAs in Bacillus subtilis:A review on regulatory mechanism and applications in synthetic biology

Bacteria exhibit a rich repertoire of RNA molecules that intricately regulate gene expression at multiple hierarchical levels,including small RNAs(sRNAs),riboswitches,and antisense RNAs.Notably,the majority of these regulatory RNAs lack or have limited protein-coding capacity but play pivotal roles in orchestrating gene expression by modulating transcription,post-transcription or translation processes.Leveraging and redesigning these regulatory RNA elements have emerged as pivotal strategies in the domains of metabolic engineering and synthetic biology.While previous investigations predominantly focused on delineating the roles of regulatory RNA in Gram-negative bacterial models such as Escherichia coli and Salmonella enterica,this review aims to summarize the mechanisms and functionalities of endogenous regulatory RNAs inherent to typical Gram-positive bacteria,notably Bacillus subtilis.Furthermore,we explore the engineering and practical applications of these regulatory RNA elements in the arena of synthetic biology,employing B.subtilis as a foundational chassis.

Construction of the underlying circRNA-miRNA-mRNA regulatory network and a new diagnostic model in ulcerative colitis by bioinformatics analysis

BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.

New horizons of regulatory RNA

Genetic information flows from DNA to protein through RNA in the central dogma.Different RNA species are known to accomplish essential tasks of protein encoding(mRNAs),amino acid loading(tRNAs),and translation machinery assembly(rRNAs).However,on top of these well-known roles,RNAs are central to various cellular regulatory pathways.Here we summarize newly emerging regulatory functions of RNA,specifically focusing on regulations through RNA modifications,RNP granules,and chromatin-associated regulatory RNA.In addition to being an essential building block of the central dogma,RNA can be critical to the regulation of many cellular processes.

Regulatory role of microRNA on inflammatory responses of diabetic retinopathy

The prevalence of diabetes has been increasing in the U.S., with diabetes as a significant concern for patients＇ physical and financial health. Diabetic retinopathy is the leading cause of vi- sual loss in working-age of adults and is characterized by retinal neurodegeneration and microvascular abnormalities in the eye. Hyperglycemia is one significant risk factor for diabetic retinop- athy and can result in increased inflammatory responses and vascular dysfunction. However, the molecular mechanisms un-derlying these pathologies are not fully understood. Although treatments are currently available for the patients with prolif-erative diabetic retinopathy or macular edema, including laser photocoagulation, steroids, or anti-vascular endothelial growth factor （VEGF） injections, many patients fail to respond to these therapies. Therefore, it is imperative to develop additional novel therapeutics for diabetic retinopathy.

Role of nickel-regulated small RNA in modulation of Helicobacter pylori virulence factors

Helicobacter pylori(H.pylori)is a Gram-negative bacterium that infects about half of the world's population.H.pylori infection prevails by several mechanisms of adaptation of the bacteria and by its virulence factors including the cytotoxin associated antigen A(CagA).CagA is an oncoprotein that is the protagonist of gastric carcinogenesis associated with prolonged H.pylori infection.In this sense,small regulatory RNAs(sRNAs)are important macromolecules capable of inhibiting and activating gene expression.This function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial infections.Recent discoveries have shown that nickelregulated small RNA(NikS)is a post-transcriptional regulator of virulence properties of H.pylori,including the oncoprotein CagA.Notably,high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of CagA.In addition,NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients without.With that in mind,this minireview approaches,in an accessible way,the most important and current aspects about the role of NikS in the control of virulence factors of H.pylori and the potential clinical repercussions of this modulation.

Circulating CCRR serves as potential novel biomarker for predicting acute myocardial infarction

Objective:Cold regions exhibit a high prevalence of cardiovascular disease,particularly acute myocardial infarction(AMI),which is one of the leading causes of death associated with cardiovascular conditions.Cardiovascular disease is closely linked to the abnormal expression of long non-coding RNA(lncRNA).This study investigates whether circulating levels of lncRNA cardiac conduction regulatory RNA(CCRR)could serve as a biomarker for AMI.Materials and methods:We measured circulating CCRR from whole blood samples collected from 68 AMI patients and 69 non-AMI subjects.An AMI model was established using C57BL/6 mice.Quantitative reverse transcription PCR(qRT-PCR)was used to assess CCRR expression.Exosomes were isolated from cardiomyocytes,and their characteristics were evaluated using electron microscope and nanoparticle tracking analysis.The exosome inhibitor GW4869 was employed to examine the effect of exosomal CCRR on cardiac function using echocardiography.Protein expression was detected using Western blot and immunofluorescence staining.Results:The circulating level of CCRR was significantly higher in AMI patients(1.93±0.13)than in non-AMI subjects(1.00±0.05,P<0.001).The area under the ROC curve(AUC)of circulating CCRR was 0.821.Similar changes in circulating CCRR levels were consistently observed in an AMI mouse model.Exosomal CCRR derived from hypoxia-induced cardiomyocytes and cardiac tissue after AMI were increased,a change that was reversed by GW4869.Additionally,CCRR-overexpressing exosomes improved cardiac function in AMI.Conclusion:Circulating lncRNA CCRR is a potential predictor of AMI.Exosomal CCRR plays a role in the communication between the heart and other organs through circulation.

Gene knockdown by structure defined single-stem loop small non-coding RNAs with programmable regulatory activities

Gene regulation by trans-acting small RNAs(sRNAs)has considerable advantages over other gene regulation strategies.However,synthetic sRNAs mainly take natural sRNAs(MicC or SgrS)as backbones and comprise three functional elements folding into two or more stem-loop structures:an mRNA base pairing region,an Hfq-binding structure,and a rho-independent terminator.Due to limited numbers of natural sRNAs and complicated backbone structures,synthetic sRNAs suffer from low activity programmability and poor structural modularity.Moreover,natural sRNA backbone sequences may increase the possibility of unwanted recombination.Here,we present a bottom-up approach for creating structure defined single-stem loop small non-coding RNAs(ssl-sRNAs),which contain a standardized scaffold of a 7 bp-stem-4 nt-loop-polyU-tail and a 24 nt basing pairing region covering the first eight codons.Particularly,ssl-sRNA requires no independent Hfq-binding structure,as the polyU tail fulfills the roles of binding Hfq.A thermodynamic-based scoring model and a web server sslRNAD(http://www.kangzlab.cn/)were developed for automated design of ssl-sRNAs with well-defined structures and programmable activities.ssl-sRNAs displayed weak polar effects when regulating polycistronic mRNAs.The ssl-sRNA designed by sslRNAD showed regulatory activities in both Escherichia coli and Bacillus subtilis.A streamlined workflow was developed for the construction of customized ssl-sRNA and ssl-sRNA libraries.As examples,the E.coli cell morphology was easily modified and new target genes of ergothioneine biosynthesis were quickly identified with ssl-sRNAs.ssl-sRNA and its designer sslRNAD enable researchers to rapidly design sRNAs for knocking down target genes.

RNAirport:a deep neural network-based database characterizing representative gene models inplants

A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency.Here,we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species.We rank the intra-sample and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader.To further assign a representative 5'-end,we train the deep-learning model 5'leaderP to learn aTsS-mediated 5'-end distribution patterns from cap-analysis gene expression data.The model accurately predicts the 5'-end,confirmed experimentally in Arabidopsis and rice.The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport(http:/www.rnairport.com/leader5P/).The Stage 1 annotation of 5'-leader records 5'-leader diversity and will pave the way to Ribo-Seq open-reading frame annotation,identical to the project recently initiated by human GENCODE.