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Biogenesis, Functions, and Cancer Relationships of a Specific Circular rna: CircFoxo3

RUSSIAN JOUrnaL OF BIOORGANIC CHEMISTRY 2021年第6期47卷 1190-1200页

作者： Zhang, Cai Li, Bin Huang, Yong Gao, Shiyang Gao, Xiaochan Henan Univ Sci & Technol Coll Anim Sci & Technol Luoyang 471023 Peoples R China

Circrnas are a new type of endogenous ncrnas, and are characterized by a covalently closed continuous loop structure having no 5 ' terminal cap and 3 ' ends. With the progression of rna sequencing and the rapid growth of bioinformatics analyses, circrnas were identified across a broad range of organisms from eukaryotes, prokaryotes, microbes and viruses. Growing evidence suggests that circrnas are found to impact several pathological and physiological processes as either tumor suppressor genes or oncogenes, and play multiple biological functions in both occurrence and development of many diseases, especially in cancers. A recently identified a circrna, circFoxo3, were found to be closely associated with different cancers. Therefore, it seems that further research on circFoxo3 could facilitate the diagnosis and treatment of cancers. The current review summarized the characteristics, biogenesis and function of circrnas and focused on the latest advance concerning the roles of circFoxo3 research and their potential to be used as a promising therapeutic targets and diagnostic biomarkers.

关键词： noncoding rna circFoxo3 biogenesis function diseases cancers

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The NLRP3 inflammasome: Multiple activation pathways and its role in primary cells during ventricular remodeling

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JOUrnaL OF CELLULAR PHYSIOLOGY 2021年第8期236卷 5547-5563页

作者： Yan, Zhipeng Qi, Zhongwen Yang, Xiaoya Ji, Nan Wang, Yueyao Shi, Qi Li, Meng Zhang, Junping Zhu, Yaping Tianjin Univ Tradit Chinese Med Dept Cardiol Teaching Hosp 1 88 Changling Rd Tianjin 300381 Peoples R China Natl Clin Res Ctr Chinese Med Acupuncture & Moxib Tianjin Peoples R China

Inflammasomes are a group of multiprotein signaling complexes located in the cytoplasm. Several inflammasomes have been identified, including NLRP1, NLRP2, NLRP3, AIM2, and NLRC4. Among them, NLRP3 was investigated in most detail, and it was reported that it can be activated by many different stimuli. Increased NLRP3 protein expression and inflammasome assembly lead to caspase-1 mediated maturation and release of IL-1 beta, which triggers inflammation and pyroptosis. The activation of the NLRP3 inflammasome has been widely reported in studies of tumors and neurological diseases, but relatively few studies on the cardiovascular system. Ventricular remodeling (VR) is an important factor contributing to heart failure (HF) after myocardial infarction (MI). Consequently, delaying VR is of great significance for improving heart function. Studies have shown that the NLRP3 inflammasome plays an essential role in the process of VR. Here, we reviewed the latest studies on the activation pathway of the NLRP3 inflammasome, focusing on the effects of the NLRP3 inflammasome in primary cells during VR, and finally discuss future research directions in this field.

关键词： cardiomyocytes NLRP3 inflammasome noncoding rna vascular endothelial cells ventricular remodeling

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The effect of LINC9137 targeting miR-140-3p-NKAIN3 signal axis on the development of goose testis sertoli cells

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POULTRY SCIENCE 2024年第6期103卷 103724页

作者： Wu, Yingping Lu, Lizhi Li, Haiying Chen, Li Gu, Tiantian Zhao, Xiaoyu Yao, Yingying Li, Jiahui Xinjiang Agr Univ Coll Anim Sci Urumqi 830000 Peoples R China Zhejiang Acad Agr Sci Inst Anim Husb & Vet Med Hangzhou 310021 Peoples R China

Sertoli cells (SC) are a type of important cells in the testes, which can provide transport proteins, regulatory proteins, growth factors, and other cytokines for the spermatogenic process. They participate in the regulation of the maturation and differentiation of spermatogenic cells and play an important supporting role in the migration, proliferation, and differentiation of germ cells at all levels in the testes. Previous studies found differential expression of LINC9137, miR-140-3p, and Sodium/Potassium Transporting ATPase Interacting 3 (NKAIN3) genesin high and low sperm motility goose testicular tissues. This study investigated the effects of the LINC9137-miR-140-3p-NKAIN3 signal axis on the proliferation and apoptosis of goose testicular sertoli cells at the cellular level, respectively. The results showed that through acridine orange staining, oil red O staining, Alkaline phosphatase (AKP) staining, and RT qPCR assay, it was comprehensively identified that the cultured testicular sertoli cells were purified in vitro. Through the dual luciferase activity detection test, it was found that LINC9137 has a targeted binding site with miR-140-3p and NKAIN3. In addition, this study found that overexpression of miR-140-3p significantly inhibited the expression of LINC9137 and NKAIN3 in sertoli cells, and their expression was significantly increased when miR-140-3p was interfered with. By measuring cell proliferation activity and apoptosis related gene expression, it was found that overexpression of LINC9137 decreased cell proliferation activity (P > 0.05), while the expression level of apoptosis factor Bcl2 Associated X Protein (Bax)/B-cell lymphoma-2 (Bcl2) increased (P > 0.05). On the contrary, when interfering with LINC9137, the cell proliferation activity of sertoli cells was significantly increased (P < 0.01), and the expression level of apoptosis factor Bax/Bcl2 was significantly reduced (P < 0.05);The effect of miR-140-3p on the proliferation and apoptosis of

关键词： goose testicular development sperm motility noncoding rna Cerna

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Bioinformatic prediction of proteins relevant to functions of the bacterial OLE ribonucleoprotein complex

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MSPHERE 2024年第6期9卷 e0015924页

作者： Fernando, Chrishan M. Breaker, Ronald R. Yale Univ Dept Mol Biophys & Biochem New Haven CT 06520 USA Yale Univ Dept Mol Cellular & Dev Biol New Haven CT 06520 USA Yale Univ Howard Hughes Med Inst New Haven CT 06520 USA

OLE (ornate, large, extremophilic) rnas are members of a noncoding rna class present in many Gram-positive, extremophilic bacteria. The large size, complex structure, and extensive sequence conservation of OLE rnas are characteristics consistent with the hypothesis that they likely function as ribozymes. The OLE rna representative from Halalkalibacterium halodurans is known to localize to the phospholipid membrane and requires at least three essential protein partners: OapA, OapB, and OapC. However, the precise biochemical functions of this unusual ribonucleoprotein (RNP) complex remain unknown. Genetic disruption of OLE rna or its partners revealed that the complex is beneficial under diverse stress conditions. To search for additional links between OLE rna and other cellular components, we used phylogenetic profiling to identify proteins that are either correlated or anticorrelated with the presence of OLE rna in various bacterial species. This analysis revealed strong correlations between the essential protein-binding partners of OLE rna and organisms that carry the ole gene. Similarly, proteins involved in sporulation are correlated, suggesting a potential role for the OLE RNP complex in spore formation. Intriguingly, the Mg2+ transporter MpfA is strongly anticorrelated with OLE rna. Evidence indicates that MpfA is structurally related to OapA and therefore MpfA may serve as a functional replacement for some contributions otherwise performed by the OLE RNP complex in species that lack this device. Indeed, OLE rnas might represent an ancient rna class that enabled primitive organisms to sense and respond to major cellular stresses. IMPORTANCE OLE (ornate, large, extremophilic) rnas were first reported nearly 20 years ago, and they represent one of the largest and most intricately folded noncoding rna classes whose biochemical function remains to be established. Other rnas with similar size, structural complexity, and extent of sequence conservation have proven to

关键词： bTOR comparative genomics MpfA noncoding rna phylogenetics rna World

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Regulatory Network of Two Tumor-Suppressive noncoding rnas Interferes with the Growth and Metastasis of Renal Cell Carcinoma

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MOLECULAR THERAPY-NUCLEIC ACIDS 2019年 16卷 554-565页

作者： Zhou, Hui Tang, Kun Liu, Haoran Zeng, Jin Li, Heng Yan, Libin Hu, Junhui Guan, Wei Chen, Ke Xu, Hua Ye, Zhangqun Huazhong Univ Sci & Technol Tongji Hosp Tongji Med Coll Dept Urol Wuhan 430030 Hubei Peoples R China Hubei Inst Urol Wuhan 430030 Hubei Peoples R China

noncoding rnas (ncrnas) such as micrornas (mirnas) and long ncrnas (Incrnas) have been shown to function as pivotal regulators in the carcinogenesis of renal cell carcinoma (RCC). However, the functions and underlying mechanisms of most ncrnas in RCC are still elusive, and the crosstalks of different layers of ncrnas are seldom reported. Here we showed that miR-124 and maternally expressed gene 3 (MEG3) were both significantly reduced in RCC, and combined expression of miR-124 and MEG3 emerged as an independent prognostic factor in our RCC cohort. Overexpression of miR-124 or MEG3 inhibited cell proliferation, migration, and invasion in vitro, and restrained tumor growth in vivo. EZH2 knockdown induced the epigenetic silencing of miR-124 and MEG3 expression by H3K27me3. Besides, miR-124 directly targeted the TET1 transcript, and then the interaction resulted in the upregulation of MEG3. Furthermore, we demonstrated that MEG3 induced p53 protein accumulation, whereas p53 was a positive transcriptional regulator of the miR-124. In addition, tumor-suppressive PTPN11 was identified as a direct target of miR-124, as well as the MEG3- and p53-regulated gene. Our study identifies three crosstalks between miR-124 and MEG3, which provide a plausible link for these two ncrnas in RCC. Both ncrnas exert important antitumor effects in RCC path-ogenesis and might serve as prognostic biomarkers and molecular therapeutic targets.

关键词： EZH2 MEG3 PTPN11 methylation miR-124 noncoding rna p53 renal cell carcinoma

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Epigenetic mechanisms of bone cancer pain

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NEUROPHARMACOLOGY 2024年 261卷 110164页

作者： Ni, Chaobo Chen, Liping Hua, Bohan Han, Zixin Xu, Longsheng Zhou, Qinghe Yao, Ming Ni, Huadong Jiaxing Univ Hosp Jiaxing 1 Affiliated Hosp Dept Anesthesiol Jiaxing 314001 Zhejiang Peoples R China Jiaxing Univ Hosp Jiaxing 1 Affiliated Hosp Pain Res Ctr Jiaxing Zhejiang Peoples R China

The management and treatment of bone cancer pain (BCP) remain significant clinical challenges, imposing substantial economic burdens on patients and society. Extensive research has demonstrated that BCP induces changes in the gene expression of peripheral sensory nerves and neurons, which play crucial roles in the onset and maintenance of BCP. However, our understanding of the epigenetic mechanisms of BCP underlying the transcriptional regulation of pro-nociceptive (such as inflammatory factors and the transient receptor potential family) and anti-nociceptive (such as potassium channels and opioid receptors) genes remains limited. This article reviews the epigenetic regulatory mechanisms in BCP, analyzing the roles of histone modifications, DNA methylation, and noncoding rnas (ncrnas) in the expression of pro-nociceptive and anti-nociceptive genes. Finally, we provide a comprehensive view of the functional mechanisms of epigenetic regulation in BCP and explore the potential of these epigenetic molecules as therapeutic targets for BCP.

关键词： Epigenetic mechanisms Bone cancer pain Histone modifications DNA methylation noncoding rna

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TIMP3 involvement and potentiality in the diagnosis, prognosis and treatment of diabetic nephropathy

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ACTA DIABETOLOGICA 2021年第12期58卷 1587-1594页

作者： Casagrande, Viviana Federici, Massimo Menghini, Rossella Univ Roma Tor Vergata Dept Syst Med Rome Italy Policlin Tor Vergata Univ Dept Med Sci Ctr Atherosclerosis Rome Italy

Diabetic kidney disease, one of the most severe complications associated with diabetes, is characterized by albuminuria, glomerulosclerosis and progressive loss of renal function. Loss of TIMP3, an Extracellular matrix-bound protein, is a hallmark of diabetic nephropathy in human and mouse models, suggesting its pivotal role in renal diseases associated to diabetes. There is currently no specific therapy for diabetic nephropathy, and the ability to restore high TIMP3 activity specifically in the kidney may represent a potential therapeutic strategy for the amelioration of renal injury under conditions in which its reduction is directly related to the disease. Increasing evidence shows that diabetic nephropathy is also regulated by epigenetic mechanisms, including noncoding rna. This review recapitulates the pathological, diagnostic and therapeutic potential roles of TIMP3 and the noncoding rna (microrna, long noncoding rna) related to its expression, in the progression of diabetic nephropathy.

关键词： Diabetic nephropathy TIMP3 noncoding rna

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The mechanistic, diagnostic and therapeutic novel nucleic acids for hepatocellular carcinoma emerging in past score years

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BRIEFINGS IN BIOINFORMATICS 2021年第2期22卷 1860-1883页

作者： Zhang, Song Zhou, Ying Wang, Yanan Wang, Zhengwen Xiao, Qitao Zhang, Ying Lou, Yan Qiu, Yunqing Zhu, Feng Zhejiang Univ Affiliated Hosp 1 Zhejiang Prov Key Lab Drug Clin Res & Evaluat State Key Lab Diag & Treatment Infect DisCollabo 79 QingChun Rd Hangzhou 310000 Zhejiang Peoples R China Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310058 Zhejiang Peoples R China Zhejiang Univ Affiliated Hosp 1 Hangzhou Peoples R China Nanchang Univ Sch Life Sci Nanchang Jiangxi Peoples R China

Despite The Central Dogma states the destiny of gene as `DNA makes rna and rna makes protein', the nucleic acids not only store and transmit genetic information but also, surprisingly, join in intracellular vital movement as a regulator of gene expression. Bioinformatics has contributed to knowledge for a series of emerging novel nucleic acids molecules. For typical cases, microrna (mirna), long noncoding rna (lncrna) and circular rna (circrna) exert crucial role in regulating vital biological processes, especially in malignant diseases. Due to extraordinarily heterogeneity among all malignancies, hepatocellular carcinoma (HCC) has emerged enormous limitation in diagnosis and therapy. Mechanistic, diagnostic and therapeutic nucleic acids for HCC emerging in past score years have been systematically reviewed. Particularly, we have organized recent advances on nucleic acids of HCC into three facets: (i) summarizing diverse nucleic acids and their modification (mirna, lncrna, circrna, circulating tumor DNA and DNA methylation) acting as potential biomarkers in HCC diagnosis;(ii) concluding different patterns of three key noncoding rnas (mirna, lncrna and circrna) in gene regulation and (iii) outlining the progress of these novel nucleic acids for HCC diagnosis and therapy in clinical trials, and discuss their possibility for clinical applications. All in all, this review takes a detailed look at the advances of novel nucleic acids from potential of biomarkers and elaboration of mechanism to early clinical application in past 20 years.

关键词： noncoding rna lncrna mirna ctDNA hepatocellular carcinoma therapy

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Leader rna regulates snakehead vesiculovirus replication via interacting with viral nucleoprotein

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rna BIOLOGY 2021年第4期18卷 537-546页

作者： Qin, Xiangmou Feng, Shuangshuang Zhang, Yanwei Su, Jianguo Lin, Li Zhang, Yong-an Tu, Jiagang Huazhong Agr Univ Coll Fisheries State Key Lab Agr Microbiol Wuhan Peoples R China Qingdao Natl Lab Marine Sci & Technol Lab Marine Biol & Biotechnol Qingdao Peoples R China Zhongkai Univ Agr & Engn Coll Anim Sci & Technol Guangdong Prov Key Lab Waterfowl Hlth Breeding Guangzhou Peoples R China

Leader rna, a kind of virus-derived small noncoding rna, has been proposed to play an important role in regulating virus replication, but the underlying mechanism remains elusive. In this study, snakehead vesiculovirus (SHVV), a kind of fish rhabdovirus causing high mortality to the cultured snakehead fish in China, was used to unveil the molecular function of leader rna. High-throughput small rna sequencing of SHVV-infected cells showed that SHVV produced two groups of leader rnas (named le(group1)and le(group2)) during infection. Overexpression and knockout experiments reveal that le(group1), but not le(group2), affects SHVV replication. Mechanistically, le(group1)-mediated regulation of SHVV replication was associated with its interaction with the viral nucleoprotein (N). Moreover, the nucleotides 6-10 of le(group1)were identified as the critical region for its interaction with the N protein, and the amino acids 1-45 of N protein were proved to confer its interaction with the le(group1). Taken together, we identified two groups of SHVV leader rnas and revealed a role in virus replication for one of the two types of leader rnas. This study will help understand the role of leader rna in regulating the replication of negative-stranded rna viruses.

关键词： Leader rna snakehead vesiculovirus nucleoprotein noncoding rna virus replication

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Identification of cerna and candidate genes related to fertility conversion of TCMS line YS3038 in wheat

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PLANT PHYSIOLOGY AND BIOCHEMISTRY 2021年 158卷 190-207页

作者： Han, Yucui Zhao, Yue Wang, Hairong Zhang, Yiyang Ding, Qin Ma, Lingjian Northwest A&F Univ Coll Agron Yangling 712100 Shaanxi Peoples R China Northwest A&F Univ Coll Hort Yangling 712100 Shaanxi Peoples R China

Previous studies have indicated that noncoding rnas are important factors in gene functions. To explore the mechanism of male sterility of YS3038, the sterile genes were mapped, and based on previous work, the expression of long noncoding rnas (lncrnas), circular rnas (circrnas), and their target genes was studied. Weighted gene coexpression network analysis (WGCNA) and competitive endogenous rna (cerna) analysis were further performed for differentially expressed noncoding rnas and target genes. At last, the candidate genes were silenced by barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) to prove their function. The sterile genes were mapped on chromosomes 1B and 6B based on chip mix pool analysis, and one major effect QTL (27.3190% variation) was found based on SSR primers. The WGCNA analysis revealed that the dark turquoise and steel blue modules were highly correlated with anther development and fertility conversion, respectively. The cerna analysis showed that a total of 184 rnas interacted with each other, including 115 mrnas, 55 micrornas (mirnas), eight circrnas, and six lncrnas. Finally, the seed setting rate of the plant was significantly decreased after fatty acyl-CoA reductase 5 silencing. This study provides breeders with a new option for the development of thermosensitive cytoplasmic male-sterile (TCMS) wheat lines, which will favor the sustainable development of two-line hybrid wheat.

关键词： Triticum aestivum L. Thermosensitive cytoplasmic male sterility noncoding rna Differential expression QTL Gene silencing

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