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Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers

Xuefei Ma, Wei Zhang, Rong Zhang, Jingming Li, Shufen Li, Yunlin Ma, Wen Jin, Kankan Wang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 330-343 doi: 10.1007/s11684-017-0557-0

摘要： Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.

关键词： long noncoding RNA     CRNDE     alternative splicing    

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Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the

《医学前沿（英文）》   页码 924-938 doi: 10.1007/s11684-023-1004-z

摘要： Long noncoding RNAs (lncRNAs) play a crucial regulatory role in the development and progression of multiple cancers. However, the potential mechanism by which lncRNAs affect the recurrence and metastasis of ovarian cancer remains unclear. In the current study, the lncRNA LOC646029 was markedly downregulated in metastatic ovarian tumors compared with primary tumors. Gain- and loss-of-function assays demonstrated that LOC646029 inhibits the proliferation, invasiveness, and metastasis of ovarian cancer cells in vivo and in vitro. Moreover, the downregulation of LOC646029 in metastatic ovarian tumors was strongly correlated with poor prognosis. Mechanistically, LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling. Collectively, our results demonstrated that LOC646029 is involved in the progression and metastasis of ovarian cancer, which may be a potential prognostic biomarker.

关键词： ovarian cancer     lncRNA LOC646029     metastasis     microRNA 627-3p     SPRED1    

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Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

《医学前沿（英文）》 2022年 第16卷 第2期   页码 176-184 doi: 10.1007/s11684-021-0885-y

摘要： Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

关键词： small noncoding RNAs     epigenetic inheritance     paternal intergenerational inherence     extracellular vesicles    

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非编码RNA及其在组织工程中的潜在应用

李石营, 钱天梅, 王星辉, 刘杰, 顾晓松

《工程（英文）》 2017年 第3卷 第1期   页码 3-15 doi: 10.1016/J.ENG.2017.01.005

摘要： 非编码RNA(ncRNA) 是不编码蛋白质的功能性RNA 分子，它们可以调节细胞的行为、改变组织的生物学环境。

关键词： 组织工程     非编码RNA(ncRNA)     microRNA(miRNA)     神经     皮肤     肝脏     血管系统     肌肉    

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Global transcriptome analysis for identification of interactions between coding and noncoding RNAs during

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《医学前沿（英文）》 2016年 第10卷 第3期   页码 297-310 doi: 10.1007/s11684-016-0452-0

摘要：

Studies on coding genes, miRNAs, and lncRNAs during erythroid development have been performed in recent years. However, analysis focusing on the integration of the three RNA types has yet to be done. In the present study, we compared the dynamics of coding genes, miRNA, and lncRNA expression profiles. To explore dynamic changes in erythropoiesis and potential mechanisms that control these changes in the transcriptome level, we took advantage of high throughput sequencing technologies to obtain transcriptome data from cord blood hematopoietic stem cells and the following four erythroid differentiation stages, as well as from mature red blood cells. Results indicated that lncRNAs were promising cell marker candidates for erythroid differentiation. Clustering analysis classified the differentially expressed genes into four subtypes that corresponded to dynamic changes during stemness maintenance, mid-differentiation, and maturation. Integrated analysis revealed that noncoding RNAs potentially participated in controlling blood cell maturation, and especially associated with heme metabolism and responses to oxygen species and DNA damage. These regulatory interactions were displayed in a comprehensive network, thereby inferring correlations between RNAs and their associated functions. These data provided a substantial resource for the study of normal erythropoiesis, which will permit further investigation and understanding of erythroid development and acquired erythroid disorders.

关键词： erythroid differentiation     hematopoietic stem cell     RNA-seq     miRNA     lncRNA    

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Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation

Jing Ma, Shiyu Chen, Lili Hao, Wei Sheng, Weicheng Chen, Xiaojing Ma, Bowen Zhang, Duan Ma, Guoying Huang

《医学前沿（英文）》 2021年 第15卷 第1期   页码 91-100 doi: 10.1007/s11684-020-0778-5

摘要： Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.

关键词： congenital heart disease     Gene Expression Omnibus     lncRNA SAP30-2:1     cell proliferation     RNA immunoprecipitation     HAND2    

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Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major

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《医学前沿（英文）》 2017年 第11卷 第1期   页码 74-86 doi: 10.1007/s11684-017-0503-1

摘要：

β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 (8 × 60 K, Arraystar) was used to detect changes in long non-coding RNAs (lncRNAs) and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups. Compared with normal controls, 1424 and 2045 lncRNAs were up- and downregulated, respectively, in β-thalassemia major patients, whereas 623 and 349 lncRNAs were up- and downregulated, respectively, in β-thalassemia minor patients. Compared with β-thalassemia minor group, 1367 and 2356 lncRNAs were up- and downregulated, respectively, in β-thalassemia major group. We selected five lncRNAs that displayed altered expressions (DQ583499, X-inactive specific transcript (Xist), lincRNA-TPM1, MRFS16P, and lincRNA-RUNX2-2) and confirmed their expression levels in all samples using real-time polymerase chain reaction. Based on coding-non-coding gene co-expression network and gene ontology biological process analyses, several signaling pathways were associated with three common organ systems exhibiting β-thalassemia phenotypes: hematologic, skeletal, and hepatic systems. This study implicates that abnormal expression levels of lncRNAs and mRNA in β-thalassemia cases may be correlated with its various clinical phenotypes.

关键词： β-thalassemia     long non-coding RNA     mRNA     phenotypic heterogeneity     pathway    

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Ribozyme and the mechanisms that underlie RNA catalysis

Timothy J. Wilson,Yijin Liu,David M. J. Lilley

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 178-185 doi: 10.1007/s11705-016-1558-2

摘要： Ribozymes are widespread, and catalyze some extremely important reactions in the cell. Mechanistically most fall into one of two classes, using either metal ions or general acid-base catalysis. The nucleolytic ribozymes fall into the latter class, mostly using nucleobases. A sub-set of these use a combination of guanine base plus adenine acid to catalyze the cleavage reaction. New ribozymes are still being discovered at regular intervals and we can speculate on the potential existence of ribozymes that catalyze chemistry beyond phosphoryl transfer reactions, perhaps using small-molecule coenzymes.

关键词： RNA catalysis     RNA structure     catalytic mechanism    

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抗RNA病毒相关生物材料

姚康德,尹玉姬,张宝连,赵立国

《中国工程科学》 2003年 第5卷 第7期   页码 17-23

摘要：

在介绍RNA病毒结构、生殖、复制和转录的基础上，综述了抗病毒策略，其中包括抗SARS药物设计，RNA干扰，DNA疫苗释放系统，调控蛋白与糖胺聚糖衍生物或类似物相互作用，天然药物及肺泡组织工程等。这些实例涵盖了RNA病毒与蛋白质、DNA及多糖等生物材料的相互作用。生物材料作为基质或载体正在向细胞或/和基因活化的第三代生物材料发展，可望在抗病毒中发挥作用。

关键词： 抗RNA病毒     蛋白质     DNA     多糖     生物材料    

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基于RNA的生物防治——一种作物保护新模式 Review

Matthew Bramlett, Geert Plaetinck, Peter Maienfisch

《工程（英文）》 2020年 第6卷 第5期   页码 522-527 doi: 10.1016/j.eng.2019.09.008

摘要： 在过去的几年中，RNA干扰（RNAi）过程被认为是一种非常有前景的新方法，可作为化学和生物害虫防治剂、植物保护剂等叶面喷施、土壤或种子处理的补充。基于RNA的活性成分（AI）具有独特的作用方式，可以通过基因修饰（GM）和生物防治两种途径来实现。由于基于RNA的AI可利用自然过程来发挥控制作用，同时它们具有高度选择性，降低了非目标生物（NTO）的风险，因此基于RNA的AI有望提供未来作物保护剂所需要的选择性和可持续性。本文讨论了基于RNA的生物防治的替代方案在作物保护中的优势和局限性，以及RNA生物防治科罗拉多马铃薯甲虫（CPB）、玉米根虫（CRW）和大豆臭虫（SSB）的最新研究进展。在实现各种基于RNA的产品及其广泛使用和应用的道路上，仍然存在许多挑战。尽管如此，我们仍可预期到，基于RNA的AI将成为有价值的新工具，以补充当前的农作物保护解决方案。

关键词： 基于RNA的生物防治     RNA干扰（RNAi）     科罗拉多马铃薯甲虫（CPB）     玉米根虫（CRW）     大豆臭虫（SSB）    

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敲低特异性环状非编码RNA显著抑制骨肉瘤的进展 Article

王世东, 张红亮, 李博, 陈成龙, 任婷婷, 黄怡, 刘凯, 李敬敬, 郭卫

《工程（英文）》 2023年 第21卷 第2期   页码 187-193 doi: 10.1016/j.eng.2021.12.007

摘要： 异常表达的非编码环状RNA（circRNA）对骨肉瘤的发生和发展至关重要。本研究的目的是探索一种新的circRNA circ_000203 在骨肉瘤中的表达和作用，阐明其潜在机制。

关键词： 非编码RNA     骨肉瘤     circRNA     分子机制     敲低    

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Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages

LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao

《医学前沿（英文）》 2008年 第2卷 第2期   页码 166-170 doi: 10.1007/s11684-008-0030-1

摘要： This study aims to demonstrate that blocking the receptor-interacting protein2 (Rip2) expression can decrease inflammatory cytokine production by macrophage and protect mice from endotoxin lethality. Murine Rip2 small interfering RNA (siRNA) plasmids were constructed and transfected into macrophage and Rip2 expression was detected with reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Cell proliferation was assayed with MTT. TNF-? concentration was assayed with ELISA and high-mobility group box 1 protein (HMGB1) level with semi-quantitative western blot after lipopolysaccharide (LPS) stimulation. LPS challenge was given after the plasmids were injected into mice and the survival rate was calculated. Rip2 siRNA plasmid could block the mRNA and protein expression of Rip2 and promote cell proliferation. Blocking Rip2 could attenuate LPS-induced TNF-? and HMGB1 production. The HMGB1 expression in the liver decreased to (40.21 ± 11.03) pg/g, and serum TNF-? level decreased to (300.43 ± 59.26) ng/L ( < 0.05). The survival rate of mice from endotoxemia was also improved ( < 0.05). The results demonstrate that Rip2 siRNA plasmid can block the expression of Rip2, decrease the production of TNF-? and HMGB1 and protect mice from fatal endotoxemia.
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The critical importance of epigenetics in autoimmune-related skin diseases

《医学前沿（英文）》 2023年 第17卷 第1期   页码 43-57 doi: 10.1007/s11684-022-0980-8

摘要： Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.

关键词： epigenetics     autoimmune-related skin diseases     DNA methylation     histone modifications     noncoding RNAs    

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Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 502-508 doi: 10.1007/s11684-017-0590-z

摘要：

Although the efficacy of nucleos(t)ide analogue (NA) has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus (HBV) are integrated into the life cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA (cccDNA), particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen (HBsAg) that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a “para-functional cure,” a status nearly close to the functional cure of chronic hepatitis B, to distinguish the “functional cure” characterized as serum HBsAg loss with or without anti-HBs seroconversion.

关键词： chronic hepatitis B     serum HBV RNA     nucleos(t)ide analogs     virological response     para-functional cure    

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immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell RNA-seq

《医学前沿（英文）》 doi: 10.1007/s11684-023-1017-7

摘要： The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS3) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

关键词： single-cell RNA-seq     glioma     radial glia     primitive oligodendrocyte precursor cell     immune escape    

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标题 作者 时间 类型 操作

Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers

Xuefei Ma, Wei Zhang, Rong Zhang, Jingming Li, Shufen Li, Yunlin Ma, Wen Jin, Kankan Wang

期刊论文

Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the

期刊论文

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

期刊论文

非编码RNA及其在组织工程中的潜在应用

李石营, 钱天梅, 王星辉, 刘杰, 顾晓松

期刊论文

Global transcriptome analysis for identification of interactions between coding and noncoding RNAs during

null

期刊论文

Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation

Jing Ma, Shiyu Chen, Lili Hao, Wei Sheng, Weicheng Chen, Xiaojing Ma, Bowen Zhang, Duan Ma, Guoying Huang

期刊论文

Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major

null

期刊论文

Ribozyme and the mechanisms that underlie RNA catalysis

Timothy J. Wilson,Yijin Liu,David M. J. Lilley

期刊论文

抗RNA病毒相关生物材料

姚康德,尹玉姬,张宝连,赵立国

期刊论文

基于RNA的生物防治——一种作物保护新模式

Matthew Bramlett, Geert Plaetinck, Peter Maienfisch

期刊论文

敲低特异性环状非编码RNA显著抑制骨肉瘤的进展

王世东, 张红亮, 李博, 陈成龙, 任婷婷, 黄怡, 刘凯, 李敬敬, 郭卫

期刊论文

Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages

LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao

期刊论文

The critical importance of epigenetics in autoimmune-related skin diseases

期刊论文

Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

期刊论文

immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell RNA-seq

期刊论文