The Potential of Circular RNAs as Biomarkers in Pulmonary Arterial Hypertension Related to Congenital Heart Disease

A particular type of endogenous noncoding RNAs known as circular RNAs(circRNAs)has now become possible biomarkers for several diseases because of their stability and tissue-specific expression patterns.CircRNAs might play a role in various of biological processes.The identification of particular circRNAs dysregulated in pulmonary arterial hypertension(PAH)raises the possibility of these molecules serving as biomarkers for the disease’s early diagnosis and treatment.This review mainly summarizes the role and potential of circRNA as a future biomarker in PAH related to congenital heart disease.This study presented several potential circRNA targets as diagnostic biomarkers for PAH,discussed their biological functions,and addressed the challenges that need to be considered for their application in clinical settings.

基于外周血circRNAs构建抑郁症严重程度的预测模型

目的基于外周血环形RNA(circular RNAs,circRNAs)表达构建抑郁症严重程度的预测模型。方法选取2022年8月至2023年8月于笔者医院就诊的抑郁症80例患者,分为轻中度组49例、重度组31例,并以40名健康人作为健康组,经基因芯片筛查,选择差异较大的5种circRNAs,进一步分析circRNAs与抑郁症严重程度的关系,分析影响抑郁症严重程度的独立危险因子,根据分析结果构建基于外周血circRNAs表达的抑郁症严重程度列线图预测模型。结果与健康组、轻中度组比较,重度组circRNA_100679、circRNA_103636相对表达量降低,circRNA_102802、circRNA_103964、circRNA_002143相对表达量升高(P<0.05)。circRNA_100679、circRNA_103636与抑郁症严重程度呈负相关(r=-0.594、-0.512,P<0.05),CircRNA_102802、circRNA_103964、circRNA_002143与抑郁症严重程度呈正相关(r=0.603、0.425、0.412,P<0.05)。CircRNA_100679、circRNA_102802、circRNA_103636、circRNA_103964、circRNA_002143、家族精神疾病史、5-羟色胺(5-hydroxytryptamine,5-HT)均为抑郁症严重程度的危险因子(P<0.05)。基于外周血circRNAs等危险因子构建的列线图预测模型的预测曲线下面积为0.900(95%CI:0.811~0.945),模型区分度较好,内部验证一致性较高。结论构建基于circRNAs表达的抑郁症严重程度的列线图模型预测价值良好,可为临床抑郁症严重程度的诊断提供参考。

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.

人牙髓干细胞向成牙本质细胞分化中circRNAs差异表达的研究

目的:检测人牙髓干细胞(DPSCs)向成牙本质细胞分化过程中环状RNA(circRNA)的表达差异。方法:临床分离获取健康的牙髓组织,CD酶消化得到牙髓原代细胞,用鼠抗人STRO-1单克隆抗体孵育人牙髓细胞,用免疫磁珠分选出人DPSCs。用茜素红和碱性磷酸酶试剂鉴定DPSCs分化能力;采用Arraystar基因芯片检测circRNAs在DPSCs成牙本质细胞诱导分化过程中的差异,并做生物信息学分析。结果:在成牙本质诱导的DPSCs组中,有42个circRNAs上调,101个circRNAs下调。GO注释显示差异表达的基因主要参与核转运,胆固醇代谢等生物学过程。Pathway注释显示其主要调节泛素介导的蛋白质水解、癌症途径以及甾体生物合成等途径,调控Wnt、PI3K-Akt和MAPK等多种信号通路。结论:差异表达的circRNAs可能影响DPSCs向成牙本质分化。

犬弓首蛔虫感染比格犬不同阶段肝circRNAs表达模式的分析

旨在探究终末宿主肝环状RNA(circRNAs)在犬弓首蛔虫诱导致病过程中的潜在调控作用。18只6~7周龄的比格犬被平均分为3组(感染后0.5 d组、感染后1 d组和感染后36 d组),每组包括感染和对照各3只,分别于感染后对应的时间点收集肝样品。提取感染和对照组肝的总RNA,利用高通量RNA测序,构建circRNA文库,对差异表达的circRNAs进行分析,并对差异表达circRNAs的亲本基因进行GO注释和KEGG富集分析。随机选取9个差异表达circRNAs进行实时荧光定量PCR验证。结果显示,与对照组相比,在感染后0.5、1和36 d分别有94、103和84个犬肝的差异表达circRNAs。Venn图显示,3个感染阶段没有共同表达的差异circRNAs;GO和KEGG分析显示,差异表达的circRNAs参与了宿主肝免疫与炎症的相关通路,其中差异表达的circRNA novel_circ_0016108、novel_circ_0016184和novel_circ_0027468与犬弓首蛔虫引起的天然免疫相关;novel_circ_0002212参与了犬弓首蛔虫引起的肝炎症反应;novel_circ_0002212和novel_circ_0019907在宿主肝抵抗犬弓首蛔虫侵袭的过程中发挥作用。RT-qPCR验证结果显示大多数差异表达的circRNAs与高通量测序结果一致。结果表明,肝circRNAs在犬弓首蛔虫感染终末宿主的过程中发挥着重要作用,这为进一步探究犬弓首蛔虫与宿主之间的相互作用提供了新的信息,并且也为促进疾病干预措施的制定提供参考。

Circular RNAs in colorectal cancer:Possible roles in regulation of cancer cells

Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC, becoming a serious health problem. In this context, a potential biomarker for the early detection of CRC has recently gained attention. Circular RNAs(circ RNA), a re-discovered, abundant RNA specie, is a type of noncoding covalent closed RNAs formed from both exonic and intronic sequences. These circular molecules are widely expressed in cells, exceeding the abundance of the traditional linear m RNA transcript. They can regulate gene expression, acting as real sponges for mi RNAs and also regulate alternative splicing or act as transcriptional factors and inclusive encoding for proteins. However, little is known about circ RNA and its relationship with CRC. In this review, we focus on the biogenesis, function and role of these circ RNAs in relation to CRC, including their potential as a new biomarker.

Circular RNAs and human glioma

As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.

Novel circular RNAs expressed in brain microvascular endothelial cells after oxygen-glucose deprivation/recovery

Circular RNAs (circRNAs) are generated by head-to-tail splicing and are ubiquitously expressed in all multicellular organisms. Their important biological functions are increasingly recognized. Cerebral ischemia reperfusion injury-induced brain microvascular endothelial cell dysfunction is an initial stage of blood-brain barrier disruption. The expression profile and potential function of circRNAs in brain microvascular endothelial cells is unknown. Rat brain microvascular endothelial cells were extracted and cultured in glucose-free medium for 4 hours with 5% CO2 and 95% N2, and the medium was then replaced with complete growth medium for 6 hours. The RNA in these cells was then extracted. The circRNA was identified by Find_circ and CIRI2 software. Functional and pathway enrichment analysis of genes that were common to differentially expressed mRNAs and circRNA host genes was performed by the Database for Annotation, Visualization and Integrated Discovery Functional Annotation Tool. Miranda software was used to predict microRNAs that were potentially sponged by circRNAs. Furthermore, cytoscape depicted the circR-NA-microRNA interaction network. The results showed that there were 1288 circRNAs in normal and oxygen-glucose deprived/recovered primary brain microvascular endothelial cells. There are 211 upregulated and 326 downregulated differentially expressed circRNAs. The host genes of these differentially expressed circRNAs overlapped with those of differentially expressed mRNAs. The shared genes were further studied by functional enrichment analyses, which revealed that circRNAs may contribute to calcium ion function and the cyclic guanosine 3′,5′-monophosphate (CAMP) dependent protein kinase (PKα) signaling pathway. Next, quantitative reverse transcription polymerase chain reaction assays were performed to detect circRNA levels transcribed from the overlapping host genes. Eight out of the ten circRNAs with the highest fold-change identified by sequencing were successfully verified. Subsequently, the circRNA-microRNA interaction networks of these eight circRNAs were explored by bioinformatic analysis. These results demonstrate that altered circRNAs may be important in the pathogenesis of cerebral ischemia reperfusion injury and consequently may also be potential therapeutic targets for cerebral ischemia diseases. All animal experiments were approved by the Chongqing Medical University Committee on Animal Research, China (approval No. CQMU20180086) on March 22, 2018.

Clinical value of circular RNAs and autophagy-related mi RNAs in the diagnosis and treatment of pancreatic cancer

Background:Circular RNAs(circRNAs)are a special group of long-chain and non-coding RNAs characterized by a closed-loop structure without 3’and 5’polarity.In recent years,studies have demonstrated that circRNAs act as microRNA(miRNA)sponges to regulate the function of miRNAs.Increasing evidence indicates that circRNAs and targeted miRNAs are involved in the development,progression and metastasis of various cancers and drug resistance.A number of miRNAs are known to be associated with the pathogenesis,development and treatment of pancreatic cancer by regulating the autophagic activity.Data sources:A comprehensive literature search was executed in PubMed and EMBASE using the medical subject headings(MeSH)terms“Pancreatic Neoplasms”,“autophagy”,“RNA,circular”and“microRNA”.We also used text terms such as“diagnosis”,“prognosis”and“biomarker”to supplement the results.Results:Autophagy-related miRNAs is closely related to pancreatic cancer.On basis of the retrieval results,we summarized the synthesis,features and functions of circRNAs and analyzed the association between autophagy-related miRNAs and pancreatic cancer.Conclusions:circRNAs act as the miRNA sponges and there is an association between miRNAs and autophagy,which provides a new concept to broaden the knowledge about the mechanisms underlying the development,progression and metastasis of pancreatic cancer.Additionally,clinical value of circRNAs and autophagy-related miRNAs in the diagnosis and treatment of pancreatic cancer would be further verified with in-depth researches.

circRNAs在肿瘤糖酵解发生发展中作用机制研究进展

近年来,环状RNA在肿瘤治疗中的作用成为了研究热点.糖酵解是肿瘤代谢中的一个重要环节,许多异常表达的环状RNA与肿瘤糖酵解过程中重要的酶类、细胞因子及信号通路都有密切的联系,它可通过结合microRNA抑制其功能,直接或间接影响下游靶蛋白的表达,达到促进或抑制肿瘤糖酵解过程,还可影响肿瘤患者对化疗药物产生的耐药性.文章综述了环状RNA通过葡萄糖转运蛋白及代谢酶、相关癌基因及转录因子、癌症相关信号通路影响肿瘤糖酵解,以及其在肿瘤治疗和耐药等方面的研究进展.

Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders

Neuropsychiatric disorders represent a set of severe and complex mental illnesses,and the exact etiologies of which are unknown.It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders.Currently,the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment,because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness.Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure.In recent years,there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs.In the brain,circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts.They are highly active at neuronal synapses.These features make circRNAs uniquely crucial for understanding brain health,disease,and neuropsychiatric disorders.This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders.In addition,we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders.The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders.

针刺调控CIRI大鼠缺血侧海马组织差异表达circRNAs的功能研究

目的:探讨针刺对脑缺血再灌注损伤(CIRI)大鼠脑组织的保护作用,观察针刺对CIRI大鼠缺血侧海马组织环状RNAs(circRNAs)差异表达的影响,并对其进行基因本体(GO)分析。方法:6~8周龄SD大鼠54只,运用随机数字法随机分为造模组和假手术组(sham组),造模成功后再随机分为模型组(model组)和针刺组(AC组),每组18只。采用改良Longa线栓法制备大脑中动脉闭塞再灌注(MCAO/R)模型,激光散斑成像仪监测造模前、MCAO手术后及再灌注后脑血流量,假手术组只剥离血管,不插入线栓;干预期间模型组和假手术组只捆绑不针刺,针刺组捆绑+针刺。采用改良加西亚(Garcia)评分法对神经功能进行评定,TTC染色法检测脑梗死面积,Western blot法检测神经元核抗原(NeuN)的表达,尼氏染色法观察缺血侧海马组织神经元损伤程度,基因芯片微阵列分析筛选出缺血侧海马组织差异表达的circRNAs,并对模型组/假手术组、针刺组/模型组共同差异表达circRNAs的来源基因进行GO分析。结果:与假手术组比较,模型组大鼠脑梗死面积比显著升高(P<0.01),Garcia神经功能评分、NeuN表达量和海马CA1区尼氏染色阳性细胞数显著降低(P<0.05或P<0.01);与模型组比较,针刺组脑梗死面积比显著降低(P<0.01),神经功能评分、NeuN表达量和尼氏染色阳性细胞数显著升高(P<0.05或P<0.01)。芯片筛选结果显示,与假手术组比较,模型组上调的circRNAs个数为288,下调个数为315;与模型组比较,针刺组上调的差异表达circRNAs个数为33,下调个数为18(FC>1.25,P<0.05);其中模型组/假手术组、针刺组/模型组共同差异表达的circRNAs个数为23个;GO分析显示共同差异表达circRNAs的来源基因功能涉及神经系统发育,神经元的产生、发育、分化及投射,头部、大脑及海马的发育,突触的形成、发育、延伸及运输等。结论:CIRI大鼠缺血侧海马组织circRNAs在造模后及针刺干预后均存在差异表达。针刺能显著改善CIRI大鼠的神经功能和脑梗死面积,减轻海马组织神经元损伤,其机制可能与针刺调控缺血侧海马组织多种circRNAs的差异表达及激发其促进神经元发育分化、抗神经损伤等功能有关。

CircRNAs在骨关节炎中的研究进展

骨关节炎(OA)是一种最普遍的与年龄相关的关节疾病,以慢性炎症、进行性关节软骨破坏和软骨下骨硬化为特征。骨关节炎的发病机制尚不明确,导致缺乏有效的预防和治疗方法,目前保守治疗并不能改善疾病预后,而手术治疗费用高昂,患者承受痛苦较大。环状RNA(circRNAs)是一类存在于真核生物的非编码RNA,参与调节基因表达,近年来研究发现它们在各种疾病中发挥着重要作用,成为新的研究热点,而它们是否参与骨骼系统疾病的病理过程却鲜有研究。本篇综述中,我们简要概述,并总结目前circRNAs在OA发生发展中以及治疗方面的作用和病理意义,以期为OA的治疗提供理论基础及新的靶点和新的治疗方法。

先天性心脏病新生儿血浆circRNAs芯片数据的生物信息学分析

目的利用高通量检测技术探讨新生儿先天性心脏病(CHD)的发病机制。方法将CHD新生儿血清与正常健康新生儿血清各3份进行配对分析,用微阵列探针进行环状RNA(circRNAs)检测。结果共检测到1711个circRNAs,其中差异表达的circRNAs 375个,在CHD新生儿血清中表达上调的circRNAs 115个,下调的circRNAs 260个(FDR>2,P<0.05)。通过美国Arraystar公司的微小RNA(miRNA)结合位点预测软件,该研究对每个差异表达的circRNA预测5个高匹配值的miRNA结合位点,375个差异表达的circRNAs预测结合了1546个miRNAs对14个miRNAs的靶基因进行信号通路分析,其中富集总分位于前3位的通路局灶性黏连、肌动蛋白细胞骨架调节、血管平滑肌收缩均与CHD的病理相关。通过hsa_circ_091419/miR-145/mRNA的网络图构建,该研究预测CHD相关的靶基因其34个,包括hsa-miR-145-3p的靶基因ITGB8。结论CHD的发病机制可能与circRNA和miRNA的上调或下调及circRNA-miRNA的共表达密切相关,具体涉及多种途径和多种细胞分子生物学过程的调控。

Role of circular RNAs in gastric cancer: Recent advances and prospects

Circular RNA(circRNA)is a newly discovered non-coding RNA with special structure,which is widely expressed in eukaryotic organisms and mainly located in the cytoplasm.circRNAs participate in gene regulation by working as miRNA sponges that block the inhibitory effect of miRNA on its target genes.In addition,circRNAs can bind to RNA binding proteins to regulate gene expression.Based on characteristics of stability,expression specificity and participation in gene regulation,circRNAs are expected to be biomarkers for early diagnosis of cancer or potential targets for cancer therapy.With the help of bioinformatics analysis,circRNA microarray analysis and high-throughput sequencing technology,more circRNAs were discovered to participate in the progression of gastric cancer(GC)over the past three years.This article gives an overview of these recent research focusing on the roles of circRNAs in GC and highlights the advances.

Circular RNAs: New Players in Gene Regulation

The existence of circular RNAs (circRNAs) was demonstrated over 30 years ago. They did not gain much interest at the time because they appeared to be relatively rare when compared to the abundance of the canonical linear RNAs. However, more recent evidence suggests that circRNAs are abundant in cells and tissues and possess intriguing biological properties. These recent developments have renewed our interest in this novel class of molecules. This report will provide an overview of circRNAs, discuss how they may modify our understanding of gene regulation and indicate their most likely relevance to health. The circRNAs from viruses, bacteria and archaea are not in the scope of this report, and we focused this review on circRNAs in eukaryotes.

A genome-wide landscape of mRNAs,lncRNAs,and circRNAs during subcutaneous adipogenesis in pigs

Background: Preadipocyte differentiation plays a critical role in subcutaneous fat deposition in pigs.However,the roles of different RNAs,such as messenger RNAs(mRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs) in the differentiation process of subcutaneous preadipocytes,are still largely unclear.In the present study,a transcriptome analysis,including the analysis of mRNAs,lncRNAs,and circRNAs,during different differentiation stages,namely,day 0(D0),day 2(D2),day 4(D4),and day 8(D8),of subcutaneous preadipocytes from Chinese Erhualian pigs was performed.Results: A total of 1554,470,1344,1777,and 676 differentially expressed(DE) mRNAs,112,58,95,136,and 93 DE lncRNAs,and 902,787,710,932,and 850 DE circRNAs were identified between D2 and D0,between D4 and D2,between D8 and D4,between D4 and D0,and between D8 and D0,respectively.Furthermore,functional enrichment analysis showed that the common DE mRNAs during the entire differentiation process were mainly involved in lipid metabolic and cell differentiation processes.Additionally,co-expression network analysis identified the potential lncRNAs related to adipogenesis,e.g.,MSTRG.131380 and MSTRG.62128.Conclusions: Our study provides new insights of the expression changes of RNAs during adipogenic differentiation,which might contribute to the phenotype of subcutaneous adipogenesis.These results greatly improve our understanding of the molecular mechanisms regulating subcutaneous fat deposition in pigs.

Genome-wide map of N6-methyladenosine circular RNAs identified in mice model of severe acute pancreatitis

BACKGROUND Severe acute pancreatitis(SAP)is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options.N6-methyladenosine(m6A)modification of circRNAs plays important roles in physiological and pathological processes.However,the roles of m6A circRNA in the pathological process of SAP remains unknown.AIM To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP.METHODS The SAP in C57BL/6 mice was induced using 4%sodium taurocholate salt.The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing.The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNAmicroRNA networks.The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP.RESULTS Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing,of which 32 were upregulated and 25 downregulated.Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP,such as regulation of autophagy and protein digestion.In m6A circRNA–miRNA networks,several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs,such as miR-24-3p,miR-26a,miR-92b,miR-216b,miR-324-5p and miR-762.Notably,the total m6A level of circRNAs was reduced,while the demethylase alkylation repair homolog 5 was upregulated in SAP.CONCLUSION m6A modification of circRNAs may be involved in the pathogenesis of SAP.Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.

Circular RNAs in pulmonary hypertension:Emerging biological concepts and potential mechanism

Circular RNAs(circRNAs)are endogenous RNAs with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets.Using the most powerful RNA sequencing and bioinformatics techniques,a large number of circRNAs have been identified and further functional studies have been performed.It is known that circRNAs act as potential biomarkers,sponges for microRNAs(miRNAs)and RNA-binding proteins(RBPs),and regulators of mRNA transcription.They also participate in the translation of peptides or proteins.Many types of circRNAs are dysregulated in plasma or lung tissues,and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells(PAECs)and pulmonary artery smooth muscle cells(PASMCs),leading to pulmonary vascular remodeling in pulmonary hypertension(PH).One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge.However,other potential mechanisms of action of circRNAs are still being actively explored in PH.This paper presents a systematic review of the biogenesis,biological characterization,relevant underlying functions,and future perspectives for studies of circRNAs in the pathogenesis of PH.

Advancements in our understanding of circular and long non-coding RNAs in spinal cord injury

Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding RNAs,including both long non-coding RNAs(lncRNAs)and circular RNAs(circRNAs),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncRNAs and circRNAs are novel modulato rs of SCI pathogenesis will be discussed.