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.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis

Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

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.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.

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.

Involvement of long non-coding RNAs in pear fruit senescence under high-and low-temperature conditions

Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,may also be involved in temperature-affected fruit senescence.Based on the transcriptome and microRNA sequencings,in this study,3330 lncRNAs were isolated from Pyrus pyrifolia fruit.Of these lncRNAs,2060 and 537 were responsive to high-and low-temperature conditions,respectively.Of these differentially expressed lncRNAs,82 and 24 correlated to the mRNAs involved in fruit senescence under high-and low-temperature conditions,respectively.Moreover,three lncRNAs were predicted to be competing endogenous RNAs(ceRNAs)that interact with the microRNAs involved in fruit senescence,while one and two ceRNAs were involved in fruit senescence under high-and low-temperature conditions,respectively.A dual-luciferase assay showed that the interaction of an lncRNA with a microRNA disrupts the action of the microRNA on the expression of its target mRNA(s).Furthermore,four alternative splicing-derived lncRNAs interacted with miR172i homologies(Novel_88 and Novel_69)to relieve the repressed expression of their target and produce an miR172i precursor.Correlation analysis of microRNA expression suggested that Novel_69 is likely involved in the cleavage of the pre-miR172i hairpin to generate mature miR172i.Taken together,lncRNAs are involved in pear fruit senescence under high-or low-temperature conditions through ceRNAs and the production of microRNA.

Expression profile of long non-coding RNAs in the intestine of black rockfish Sebastes schlegelii in response to Edwardsiella tarda infection

Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that widely cultured in the coastal areas of China,Japan,and South Korea.With the expansion of aquacultural scale,various pathogens have threatened its industry and reduced its economic values.It has been reported that lncRNA were involved in the immune response and metabolic pathway in teleost,while no study is available on identification and functional analysis of lncRNAs in black rockfish so far.Herein,this study was performed to identify lncRNAs in the intestine of black rockfish after Edwardsiella tarda infection.In our results,a total of 9311 lncRNAs were identified through highthroughput sequencing,and 102 lncRNAs were significantly regulated following challenge,which were predicted to target 3348 mRNAs.Results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the se target genes showed they were function in catalytic activity,hydrolase activity,defense response and peptidase activity,which involved in metabolic pathways and immune related pathways.In addition,47 lncRNAs and 8 differentially expressed mRNAs(DEmRNAs)showed co-expression at two or more infection time points with metabolism and immunity functions.Moreover,real-time quantitative PCR(qRT-PCR)was performed to verify the reliability of sequencing gene expression analysis results.This research laid the foundation for further investigation of the regulatory roles of lncRNAs in the intestinal immune response of black rockfish.

Identification and Characterization of Long Non-Coding RNAs Involved in Sex-Related Gene Regulation in Kelp Saccharina japonica

Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorphism in haploid gametophytes.The sex of Saccharina japonica gametophytes is determined by UV sexual system.However,no results have been reported on the lncRNAs involved in the sex-related gene regulation of S.japonica.This study identified a number of lncRNAs and assessed their expression levels in male and female gametophytes.Among them,a total of 405 lncRNAs and 211 mRNAs showed differential expressions.Furthermore,the functions of target genes of differentially expressed lncRNAs(DELs)differed from those of differentially expressed genes(DEGs),suggesting that lncRNA may interact with other functional proteins,in addition to DEGs,to involve sex regulation in S.japonica.There were 32 and 90 potential cis-regulatory and trans-regulatory interactions between DELsDEGs,respectively.Five of these lncRNAs(LNC_002974,LNC_021059,LNC_038466,LNC_051584,and LNC_027400)interacted with putative male sex determination region(SDR)genes,suggesting that they act as regulators in gametophytes'sex regulation potentially.Findings from this study contribute to our understanding of the roles of lncRNAs in sex differentiation and lay the foundation for functional studies of candidate lncRNAs in the future.

Bioinformatics Analysis and Experimental Verification of Prognostic and Biological Significance of Autophagy-Related Long Non-Coding RNAs in Gastric Carcinoma

Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.

基于铜死亡相关lncRNAs的胰腺癌预后模型构建与验证

目的研究铜死亡相关lncRNAs在胰腺癌(PAAD)患者中的预后预测价值,并进一步构建预后预测模型。方法从TCGA数据库中下载胰腺癌患者的转录组测序数据和相应临床信息,通过Pearson相关性分析筛选与预后相关的铜死亡相关lncRNAs,先后利用单因素Cox回归和Lasso回归分析并进一步构建预后模型。根据模型的风险评分中位数,将所有患者分为高风险组和低风险组。通过Kaplan-Meier生存分析、亚组分析、ROC曲线分析及一致性指数分析评估模型的预后预测价值,并利用单因素和多因素回归分析验证模型的独立性。对高、低风险组的差异表达基因进行GO及KEGG功能富集分析,并对高、低风险组患者进行肿瘤突变负荷(TMB)分析、免疫治疗反应预测以及药物敏感性分析。结果通过Pearson相关性分析,确定了127个铜死亡相关的lncRNAs,先后利用单因素Cox回归分析及Lasso回归分析构建了一个基于6个铜死亡相关lncRNAs的预后预测模型。根据模型计算结果将PAAD患者队列分成高风险组和低风险组,Kaplan-Meier生存分析表明低风险组患者的生存时间要长于高风险组(P<0.05)。ROC曲线证明了该模型对胰腺癌患者预后的预测性能良好:1、3、5年ROC曲线下面积分别为0.687、0.753、0.771;基因功能富集分析表明,高、低风险组差异表达基因主要富集于免疫相关通路。此外,高风险组患者的TMB值明显大于低风险组,而TIDE评分明显低于低风险组。最后,通过药物敏感性分析发现不同组的胰腺癌患者对特定药物的敏感性存在统计学差异,对临床用药具有一定的指导意义。结论本研究基于铜死亡相关lncRNAs成功构建了一个PAAD患者预后模型,可精准预测PAAD患者的预后,并为患者的临床药物治疗选择提供个性化指导。

LncRNA NORAD通过miR-513b-5p/GREM1轴调节颅内动脉瘤血管平滑肌细胞增殖、迁移、侵袭和凋亡的作用机制

目的:探讨长链非编码RNA DNA损伤诱导的非编码RNA(LncRNA NORAD)通过miR-513b-5p/GREM1轴调节颅内动脉瘤血管平滑肌细胞(VSMC)增殖、迁移、侵袭和凋亡的机制。方法:采用实时荧光定量聚合酶链式反应(PCR)法检测人颅内动脉瘤组织和正常组织中LncRNA NORAD、miR-513b-5p及GREM1表达。体外分离培养人VSMC,随机分为对照组、LncRNA NORAD siRNA组、miR-513b-5p mimics组、共转染(LncRNA NORAD siRNA+miR-513b-5p inhibitor)组、共转染阴性对照(LncRNA NORAD siRNA阴性对照+miR-513b-5p inhibitor阴性对照)组,分组转染后,采用实时荧光定量PCR法检测各组细胞LncRNA NORAD、miR-513b-5p及GREM1 mRNA表达;采用细胞计数试剂盒(CCK-8)和免疫荧光染色检测各组细胞增殖情况;采用Hoechst 33342染色和免疫荧光染色检测各组细胞凋亡情况;采用细胞划痕实验和Transwell实验检测各组细胞迁移、侵袭情况;采用免疫印记实验检测各组细胞上皮间充质转化(EMT)标志蛋白神经钙黏素(N-cadherin)、E-钙黏素(E-cadherin)、波形蛋白(Vimentin)表达;采用双荧光素酶报告实验分析VSMC中LncRNA NORAD对miR-513b-5p、miR-513b-5p对GREM1的靶向调控。结果:与正常组织比较,颅内动脉瘤组织LncRNA NORAD、GREM1 mRNA表达明显升高(P<0.05),miR-513b-5p表达明显降低(P<0.05)。与对照组比较,LncRNA NORAD siRNA组、miR-513b-5p mimics组细胞GREM1 mRNA表达、增殖率、Ki67阳性率、迁移率、侵袭数及N-cadherin、Vimentin蛋白表达降低(P<0.05),miR-513b-5p表达、凋亡率及Bax/Bcl-2、E-cadherin蛋白表达升高(P<0.05);共转染阴性对照组各指标差异无统计学意义(P>0.05)。与LncRNA NORAD siRNA组比较,共转染组细胞GREM1 mRNA表达、增殖率、Ki67阳性率、迁移率、侵袭数及N-cadherin、Vimentin蛋白表达升高(P<0.05),miR-513b-5p表达、凋亡率及Bax/Bcl-2、E-cadherin蛋白表达降低(P<0.05)。结论:敲低LncRNA NORAD可通过上调miR-513b-5p表达而降低GREM1表达,从而抑制VSMC增殖与侵袭迁移,并促使其凋亡。

参芪复方对糖尿病GK大鼠肝脏组织mRNA、lncRNA表达谱的影响

目的应用全转录组测序与实时聚合酶链锁反应(Real-time polymerase chain reaction,RT-qPCR)技术,探索参芪复方调控糖尿病GK大鼠肝脏信使RNA(messenger RNA,mRNA)、长链非编码RNA(long non-coding RNA,lncRNA)表达谱的机制研究。方法采用高脂高糖饲料建立2型糖尿病模型,将GK大鼠随机分为模型组、参芪复方组和西药组。另将10只Wistar大鼠设为空白组,予普通饲料喂养。参芪复方组大鼠予参芪复方浸膏灌胃,西药组予西格列汀混悬液灌胃,模型组及空白组灌服生理盐水。干预12周,每周检测空腹血糖(fasting blood glucose,FBG)。运用HE染色法观察大鼠肝脏组织病理形态,在空白组、模型组和参芪复方组中每组随机选取4只大鼠进行全转录组测序,构建mRNA、lncRNA差异表达谱,分析差异基因生物学功能,并进行RT-qPCR验证。结果与空白组相比,糖尿病GK大鼠FBG显著升高(P<0.05),模型组大鼠肝脏可见肝细胞排列紊乱,边界模糊,出现弥漫空泡状改变,呈中度脂肪变性,伴见炎性浸润、弥漫水肿;与模型组相比,参芪复方组大鼠FBG在12周时明显降低(P<0.05),肝脏组织排列较整齐,脂质沉积、细胞水肿及炎细胞浸润明显减轻。全转录组结果显示,与空白组相比,模型组大鼠mRNA、lncRNA表达谱存在显著差异,决定了糖尿病大鼠生理病理上的差异表现。参芪复方可广泛调控mRNA、lncRNA的差异表达,富集分析显示参芪复方通过调控多条内分泌系统及代谢过程相关信号通路改善糖尿病,包括胰岛素分泌、非酒精性脂肪性肝病、胆固醇代谢、鞘脂代谢、胰岛素抵抗等信号通路。RT-qPCR结果显示,基因Irf1、Trim30、Tmcc3、Insig1与转录组结果一致,转录组准确性较高。结论参芪复方发挥调节血糖及改善肝脏脂质沉积、水肿的作用,可能与广泛调控mRNA、lncRNA的差异表达有关。

LncRNA MAFG-AS1:恶性肿瘤的潜在生物标志物和治疗靶点

长链非编码RNA(long non-coding RNAs,LncRNAs)在肿瘤发展中的调控作用已引起广泛关注。LncRNA MAFG-AS1是一种新型的致癌长链非编码RNA,在肺癌、乳腺癌和肝细胞癌等多种肿瘤组织中高表达,与肿瘤细胞增殖、迁移、侵袭等恶性行为密切相关。此外,大量证据表明,LncRNA MAFG-AS1的上调与肿瘤患者的临床病理分期和不良生存预后有关。本文系统总结了近年来LncRNA MAFG-AS1在各种肿瘤中的表达、生物学功能、分子机制和临床意义的研究,并强调了LncRNA MAFG-AS1可作为新型诊断、预后生物标志物,以及癌症治疗的重要靶标。

桃红四物汤对大脑中动脉闭塞大鼠lncRNA表达的影响

目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照组、MCAO组和MCAO+THSWD组各获得3个大脑半球组织。采用RNA测序技术鉴定三组中的lncRNA基因表达。鉴定了THSWD调节的lncRNA基因,然后构建了THSWD调节的lncRNA-mRNA网络。通过MCODE插件鉴定lncRNA-mRNA网络的模块。基因本体(gene ontology,GO)和京都基因与基因组百科全书数据库(kyoto encyclopedia of genes and genomes,KEGG)用于分析富集的生物功能和信号通路。鉴定了THSWD调节的lncRNA的顺式和反式调控基因。采用逆转录实时定量聚合酶链式反应(RT-qPCR)验证lncRNA。分子对接用于验证lncRNA-mRNA网络靶点和通路相关蛋白结合能力。结果在MCAO大鼠中,THSWD共调节了302个lncRNA。生物信息学分析表明,一些核心lncRNA可能在THSWD治疗MCAO大鼠中发挥重要作用,此外,我们进一步发现THSWD可能也通过lncRNA-mRNA网络以及网络富集的补体和凝血级联反应等多通路治疗MCAO大鼠。分子对接结果表明,THSWD活性化合物没食子酸和苦杏仁苷与蛋白质靶点具有一定的结合能力。结论THSWD可以通过调节lncRNA保护MCAO大鼠脑损伤,为THSWD治疗缺血性中风提供了新见解。

LncRNA靶向miRNA调控子宫内膜癌发生发展的研究进展

长链非编码RNA(LncRNA)在多种肿瘤进展中扮演重要角色,MicroRNAs(miRNAs)是目前研究最多的LncRNA下游靶点,LncRNA靶向miRNAs可以直接参与肿瘤细胞生物学行为的调控。高表达或低表达的LncRNA可靶向miRNA调控下游信号通路,促进或抑制子宫内膜癌(endometrial cancer, EC)进展。随着对LncRNA/miRNA调控轴在子宫内膜癌研究的深入,LncRNA和miRNA有望成为EC诊疗的新靶点和预后标志物。本文围绕LncRNA及miRNA对EC的调控、lncRNA调控miRNA在EC中的作用进行综述。

lncRNA SNHG18在膀胱癌组织中的表达及其对细胞恶性生物学行为的影响

目的研究长链非编码RNA SNHG18基因在膀胱癌组织膀胱癌细胞系中的表达情况及其对细胞恶性生物学行为的影响。方法选取2021年8月至2022年10月行手术治疗的膀胱癌患者42例,应用RT-qPCR检测SNHG18基因在42例膀胱癌组织及3株膀胱癌细胞(5637、T24、SW780)中的表达情况;构建过表达载体pcDNA3.1-SNHG18与敲低载体SNHG18分别转染膀胱癌细胞,应用细胞增殖实验、细胞克隆形成实验、划痕实验、Transwell小室侵袭实验来观察膀胱癌细胞增殖、迁移、侵袭能力的变化。结果SNHG18在膀胱癌组织及细胞中的表达低于正常的膀胱上皮组织和膀胱上皮细胞,差异有统计学意义(P<0.05);SNHG18的表达量与性别、年龄、有无吸烟、有无高血压、有无糖尿病、有无淋巴结和远处转移及临床分期间无相关性(P>0.05);过表达SNHG18可抑制膀胱癌细胞的体外增殖、迁移和侵袭能力(P<0.05);敲低SNHG18可增强膀胱癌细胞的体外增殖、迁移和侵袭能力(P<0.05)。结论SNHG18在膀胱癌组织中表达量降低,与临床参数无关,与膀胱癌细胞增殖、迁移和侵袭能力有关。

乳腺癌中长非编码RNA及LncRNA编码多肽的功能

长非编码RNA(long non-coding RNA,lncRNA)的序列长度超过200核苷酸(nucleotide,nt),部分可编码多肽。生物信息分析和多组学技术已被用于在乳腺癌中批量鉴定lncRNA与lncRNA编码肽。本文通过在线软件分析了Spencer数据库中收录的919个lncRNA编码的乳腺癌肿瘤特异性多肽,结果显示,这些多肽涉及抗癌、抗炎和细胞穿透等活性。乳腺癌的发生发展与lncRNAs的异常表达密切相关,lncRNAs通过编码多肽、调控表观遗传、调节免疫等多种途径影响乳腺癌发展。部分lncRNA编码肽独立于lncRNA,通过表观遗传调控、抑制血管生成等途径调控乳腺癌的发展。lncRNA与lncRNA编码肽在乳腺癌的诊断与治疗中也有较大的应用潜力。因此,本文系统综述了lncRNA与lncRNA编码肽在乳腺癌发生发展与诊断治疗中的作用,对该研究领域目前存在的问题和挑战进行了分析。

lncRNA KCNQ1OT1靶向调控miR-132-5p对帕金森病细胞损伤的保护机制

目的探究长链非编码RNA KCNQ1OT1(lncRNA KCNQ1OT1)靶向调控微小RNA-132-5p(miR-132-5p)对帕金森病细胞损伤的保护机制。方法SH-SY5Y细胞通过1-甲基-4-苯基吡啶阳离子(MMP+)诱导建立帕金森病细胞模型,检测SH-SY5Y细胞中lncRNA KCNQ1OT1、miR-132-5p表达、活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平、凋亡率及Bcl-2、Bax蛋白表达,验证lncRNA KCNQ1OT1、miR-132-5p的调控关系。结果与Con组相比,MMP+组lncRNA KCNQ1OT1、miR-132-5p表达量较高(P<0.05)。低表达lncRNA KCNQ1OT1、干扰miR-132-5p表达均可减轻MMP+诱导的SH-SY5Y细胞氧化应激及炎性损伤,抑制细胞死亡,lncRNA KCNQ1OT1靶向正调控miR-132-5p表达,miR-132-5p过表达逆转了lncRNA KCNQ1OT1低表达对MMP+诱导SK-N-SH细胞氧化应激、炎症损伤及凋亡。结论lncRNA KCNQ1OT1通过靶向抑制miR-132-5p表达减轻了MMP+诱导SK-N-SH细胞氧化应激、炎症损伤,抑制了细胞凋亡。

LncRNA MIAT靶向miR-206促进食管鳞状细胞癌细胞的增殖、凋亡、迁移和侵袭的作用研究

目的 探讨长链非编码RNA(LncRNA)MIAT靶向微小RNA(miR)-206促进食管鳞状细胞癌细胞的增殖、凋亡、迁移和侵袭的作用。方法 将食管鳞状细胞癌(ESCC)细胞分为ctrl组(正常培养的ESCC细胞)、si-NC组、si-MIAT组、si-MIAT+miR-NC组和si-MIAT+miR-206 inhibitor组。实时qRT-PCR检测各组细胞MIAT、miR-206表达;CCK-8法检测细胞增殖情况;划痕实验检测细胞迁移能力;流式细胞术分析细胞凋亡情况;蛋白质印迹技术检测PCNA、MMP-9蛋白表达;双荧光素酶报告基因实验验证MIAT和miR-206的关系。结果 与ctrl组、si-NC组比较,si-MIAT组ESCC细胞中miR-206表达、细胞凋亡率升高,MIAT、OD_(450)值(24、48、72 h)、划痕愈合率、PCNA和MMP9蛋白表达降低(P<0.05);干扰LncRNA MIAT表达能降低ESCC细胞增殖、迁移、侵袭能力,提高细胞凋亡能力,MIAT靶向调控miR-206表达。结论 干扰LncRNA MIAT表达能够阻滞ESCC细胞增殖、迁移、侵袭,并促进ESCC细胞凋亡。

炎调方调控LncRNA-Miat对急性脓毒症患者免疫功能及肠道微生态的保护作用

目的 探讨炎调方调控长链非编码RNA-心肌梗死相关转录本(LncRNA-Miat)对急性脓毒症患者肠道微生态、免疫功能的保护作用。方法 选取2020年1月至2022年10月收治的急性脓毒症患者108例,根据随机数字表法分为对照组和观察组,每组54例。对照组采取常规对症治疗,观察组采用常规对症治疗+炎调方,2组均连续治疗10 d。观察组6例因意识改变或昏迷无法口服中药退出研究,为保持例数一致,对照组剔除6例,观察组和对照组各有48例进入研究。统计2组中医疗效、中医证候积分、LncRNA-Miat、磷脂酶张力蛋白同源物(PTEN)表达水平、免疫功能[核因子κB(NF-κB)mRNA、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)mRNA、白介素-1β(IL-1β)、IL-18]、肠道微生态(乳酸杆菌、肠杆菌、葡萄球菌)、28 d病死率。结果 观察组总有效率为83.33%(40/48)高于对照组62.50%(30/48),观察组发热、口渴饮冷、汗出、气喘、乏力评分低于对照组,差异均有统计学意义(P<0.05);观察组PTEN、LncRNA-Miat、NF-κB、NLRP3 mRNA、IL-1β、IL-18、葡萄球菌、肠杆菌低于对照组,乳酸杆菌高于对照组(P<0.05);与对照组相比,观察组APACHEⅡ、SOFA较低(P<0.05);2组28 d病死率对比,差异无统计学意义(P>0.05)。结论 联合炎调方治疗急性脓毒症患者,可有效调控LncRNA-Miat表达,改善患者肠道微生物平衡,提高机体免疫,缓解临床病症,促进病情好转。