Oral squamous cell carcinoma (OSCC) accounts for about 90% of oral cancers. Expression of the long noncoding rna (lncrna) maternally expressed 3 (MEG3) has previously been reported to be downregulated in OSCC, and its...
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Oral squamous cell carcinoma (OSCC) accounts for about 90% of oral cancers. Expression of the long noncoding rna (lncrna) maternally expressed 3 (MEG3) has previously been reported to be downregulated in OSCC, and its overexpression can inhibit proliferation, migration, and invasion and promote apoptosis of OSCC cells. However, the mechanism underlying MEG3 downregulation in OSCC has not been well characterized. Here we report that low expression of MEG3 is caused by H3K27me3 modification of the MEG3 gene locus, and this is associated with the poor prognosis of OSCC. Overexpression of MEG3 inhibited the proliferation and invasion of OSCC cells. We observed that MEG3 was modified by m6A and bound to YTHDC1. Enhancer-controlled genes positively regulated by MEG3 were functionally enriched for the 'negative regulation of Wnt signaling pathway' term, as determined using metascape. GATA3 was predicted to be a transcription factor for these genes, and was demonstrated to bind to MEG3. Knockdown of GATA3 countered the effects on proliferation, invasion, and increased transcription of HIC1 and PRICKLE1 induced by MEG3 overexpression. In conclusion, our data suggest that MEG3 is downregulated in OSCC due to trimethylation of H3K27 at the MEG3 gene locus. The inhibitory effect of MEG3 on proliferation and invasion of OSCC cells was dependent on the binding of GATA3.
The role of long noncoding rnas (lncrnas) regulators of toxicological responses to environmental chemicals is gaining prominence. Previously, our laboratory discovered an lncrna, sox9b long intergenic noncoding rna (s...
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The role of long noncoding rnas (lncrnas) regulators of toxicological responses to environmental chemicals is gaining prominence. Previously, our laboratory discovered an lncrna, sox9b long intergenic noncoding rna (slincR), that is activated by multiple ligands of aryl hydrocarbon receptor (AHR). Within this study, we designed a CRISPR-Cas9-mediated slincR zebrafish mutant line to better understand its biological function in presence or absence of a model AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slincR(osu3) line contains an 18 bp insertion within the slincR sequence that changes its predicted mrna secondary structure. Toxicological profiling showed that slincR(osu3) is equally or more sensitive to TCDD for morphological and behavioral phenotypes. Embryonic mrna-sequencing showed differential responses of 499 or 908 genes in slincR(osu3) in absence or presence of TCDD Specifically, unexposed slincR(osu3) embryos showed disruptions in metabolic pathways, suggesting an endogenous role for slincR. slincR(osu3) embryos also had repressed mrna levels of sox9b-a transcription factor that slincR is known to negatively regulate. Hence, we studied cartilage development and regenerative capacity-both processes partially regulated by sox9b. Cartilage development was disrupted in slincR(osu3) embryos both in presence and absence of TCDD. slincR(osu3) embryos also displayed a lack of regenerative capacity of amputated tail fins, accompanied by a lack of cell proliferation. In summary, using a novel slincR mutant line, we show that a mutation in slincR can have widespread impacts on gene expression and structural development endogenously and limited, but significant impacts in presence of AHR induction that further highlights its importance in the developmental process.
noncoding rnas are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is whether noncoding rnas are targets of medicines. Bleomycin is a natural product that cleaves DNA;ho...
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noncoding rnas are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is whether noncoding rnas are targets of medicines. Bleomycin is a natural product that cleaves DNA;however, it is known to cleave rna in vitro. Herein, an in-depth analysis of the rna cleavage preferences of bleomycinA5 is presented. Bleomycin A5 prefers to cleave rnas with stretches of AU base pairs. Based on these preferences and bioinformatic analysis, the microrna-10b hairpin precursor was identified as a potential substrate for bleomycinA5. Both in vitro and cellular experiments demonstrated cleavage. Importantly, chemical cleavage by bleomycinA5 in the microrna-10b hairpin precursors occurred near the Drosha and Dicer enzymatic processing sites and led to destruction of the microrna. Evidently, oncogenic noncoding rnas can be considered targets of cancer medicines and might elicit their pharmacological effects by targeting noncoding rna.
Mediator,a conserved multiprotein complex in animals,plants,and fungi,is a cofactor of rna polymerase II(Pol II).It is known to promote basal Pol II-mediated transcription as well as bridge sequence-specific transcrip...
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Mediator,a conserved multiprotein complex in animals,plants,and fungi,is a cofactor of rna polymerase II(Pol II).It is known to promote basal Pol II-mediated transcription as well as bridge sequence-specific transcriptional regulators and Pol II to integrate regulatory *** II transcribes not only protein-coding genes but also intergenic regions to generate noncoding rnas such as small rnas(micrornas and small interfering rnas)and long noncoding ***,two plant-specific polymerases,Pol IV and Pol V,have evolved from Pol II and play a role in the production of small interfering rnas and long noncoding rnas at heterochromatic regions to maintain genome stability through transcriptional gene silencing(TGS).Recent studies have defined the composition of the plant Mediator and evaluated its role in noncoding rna production in relationship to Pol II,Pol IV and Pol ***,we review the functions of Mediator and that of noncoding rnas generated by Pol II,Pol IV and Pol V in plants,and discuss a role of Mediator in epigenetic regulation via noncoding rna production.
Recently, it was discovered that non-protein-coding rnas (ncrnas) represent the majority of the human transcripts. Regulatory role of many classes of ncrnas is broadly recognized;however, long intronic ncrnas have rec...
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Recently, it was discovered that non-protein-coding rnas (ncrnas) represent the majority of the human transcripts. Regulatory role of many classes of ncrnas is broadly recognized;however, long intronic ncrnas have received little attention. In the past few years, evidence that intronic regions are key Sources of regulatory ncrnas has first appeared. Here we present an updated vision of the intronic ncrna world, giving special attention to the long intronic ncrnas. We summarize aspects of their expression pattern, evolutionary constraints, biogenesis, and responsiveness to physiological stimuli, and postulate their mechanisms of action. Deciphering nature's choice of different types of messages conveyed by ncrnas will shed light on the rna-based layer of regulatory processes in eukaryotic cells. (C) 2008 Elsevier Inc. All rights reserved.
rna Polymerase III is a highly specialized enzyme complex responsible for the transcription of a very distinct set of housekeeping noncoding rnas including trnas, 7SK snrna, Y rnas, U6 snrna, and the rna components of...
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rna Polymerase III is a highly specialized enzyme complex responsible for the transcription of a very distinct set of housekeeping noncoding rnas including trnas, 7SK snrna, Y rnas, U6 snrna, and the rna components of rnaseP and rnaseMRP. In this work we have utilized the conserved promoter structure of known rna Polymerase III transcripts consisting of characteristic sequence elements termed proximal sequence elements (PSE) A and B and a TATA-box to uncover a novel rna Polymerase III-transcribed, noncoding rna family found to be conserved in Caenorhabditis as well as other clade V nematode species. Homology search in combination with detailed sequence and secondary structure analysis revealed that members of this novel ncrna family evolve rapidly, and only maintain a potentially functional small stem structure that links the 5' end to the very 3' end of the transcript and a small hairpin structure at the 3' end. This is most likely required for efficient transcription termination. In addition, our study revealed evidence that canonical C/D box snornas are also transcribed from a PSE A-PSE B-TATA-box promoter in Caenorhabditis elegans. (C) 2014 Elsevier B.V. All rights reserved.
p68 and p72 are rna-binding proteins endowed with rna helicase and rna-protein complex remodeling activities. One of the rnas associated with p68/p72 is the noncoding Steroid Receptors rna Activator (SRA). Here we rev...
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p68 and p72 are rna-binding proteins endowed with rna helicase and rna-protein complex remodeling activities. One of the rnas associated with p68/p72 is the noncoding Steroid Receptors rna Activator (SRA). Here we review recent findings on the cellular processes regulated by either p68/p72 alone or in combination with SRA and discuss the transcriptional events influenced by these molecules.
noncoding rnas have drawn significant attention in carcinogenesis. In this study, we identified a novel gene named nickel-related gene1 (NRG1) associated with nickel-induced cancer. By using rapid amplification of cDN...
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noncoding rnas have drawn significant attention in carcinogenesis. In this study, we identified a novel gene named nickel-related gene1 (NRG1) associated with nickel-induced cancer. By using rapid amplification of cDNA end PCR, we obtained the full length of the cDNA. The sequence was analyzed by using related bioinformatics software and comparative genomics methods. The results showed that NRG1 was located on chromosome 2q12, within intron2 of ADAMTS6, a disintegrin and metalloproteinase with thrombospondin motifs. And, NRG1 had a high level of homology (76 %) to rat LINE1 sequence RL1.3 (long interspersed middle repetitive DNA). What's more, there was no continuous open reading frame present in NRG1 sequence. Taken together, these data demonstrate that NRG1 is a novel noncoding rna, and we predicted it may be a transposon-like gene. The identification of NRG1 emphasized the potential role of noncoding rna in nickel carcinogenesis.
作者：
Zhang, MojianPeng, ShupingCent South Univ
Hunan Canc Hosp Xiangya Sch Med Sch Basic Med Sci Changsha 410013 Hunan Peoples R China Cent South Univ
Affiliated Canc Hosp Sch Basic Med Sci Hunan Key Lab Canc MetabXiangya Sch Med Changsha 410013 Hunan Peoples R China Cent South Univ
Xiangya Hosp Key Lab Carcinogenesis & Canc Invas Chinese Minist Educ Changsha 410078 Hunan Peoples R China Cent South Univ
Xiangya Hosp 3 Dis Genome Res Ctr Hunan Key Lab Nonresolving Inflammat & Canc Changsha 410013 Hunan Peoples R China
CAPRIN1, cell cycle-associated protein 1, is an rna-binding protein in stress granules, P bodies, and messenger rna transport granules and has a high level of expression in cancer. It promotes the proliferation and in...
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CAPRIN1, cell cycle-associated protein 1, is an rna-binding protein in stress granules, P bodies, and messenger rna transport granules and has a high level of expression in cancer. It promotes the proliferation and invasion of cancer cells and enhances their glycolysis and chemoresistance. In addition, it mediates the formation of intracellular SGs in various ways when exposed to endogenous and exogenous stress. As an rna-binding protein, it not only directly binds to several mrnas associated with the cell cycle but also is the target of mirna, lncrna, and circrna. Recently, CAPRIN1 is identified as a phase-separating protein that mediates the liquid-liquid phase separation within tumor cells. Moreover, the formation of CAPRIN1-mediated phase separation is regulated by circrna and lncrna. In addition, CAPRIN1 is associated with ubiquitination, which affects the relevant characteristics of cancer cells. This review discusses the different regulatory mechanisms of CAPRIN1 in various tumors and its association with noncoding rna, suggesting its potential as an oncogenic signal and possibly as a diagnostic indicator in the future. This may provide the multifunctional characteristic insight of CAPRIN1 protein and potential therapeutic target in malignancy with high levels of CAPRIN1.
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