Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2018, Volume and Issue: 37(1)

Published: Nov. 27, 2018

Emerging evidence have illustrated the vital role of long noncoding RNAs (lncRNAs) intergenic non-protein coding RNA 00511 (LINC00511) on human cancer progression and tumorigenesis. However, LINC00511 in breast tumourigenesis is still unknown. This research puts emphasis function stemness, investigates in-depth mechanism. The lncRNA expression were measured using RT-PCR. Protein levels western blotting analysis. CCK-8, colony formation assays transwell assay performed to evaluate cell proliferation ability invasion. Sphere-formation was also for stemness. Bioinformatic analysis, chromatin immunoprecipitation (ChIP) luciferase reporter carried confirm molecular binding. be highly expressed specimens high-expression correlated with poor prognosis. Functionally, gain loss-of-functional experiments revealed that promoted proliferation, sphere-formation ability, stem factors (Oct4, Nanog, SOX2) tumor growth cells. Mechanically, functioned as competing endogenous (ceRNA) miR-185-3p positively recover E2F1 protein. Furthermore, transcription factor bind promoter region Nanog gene promote it transcription. In conclusion, our data concludes LINC00511/miR-185-3p/E2F1/Nanog axis facilitates stemness tumorigenesis, providing a insight them.

Language: Английский

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Emerging Epigenetic Regulation of Circular RNAs in Human Cancer

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 16, P. 589 - 596

Published: April 19, 2019

Circular RNAs (circRNAs) are novel members of the noncoding RNA family. Their characteristic covalent closed-loop structure endows circRNAs that much more stable than corresponding linear transcript. ubiquitous in eukaryotic cells, and their functions diverse include adsorbing microRNAs (miRNAs; acting as miRNA sponges), regulating transcription, interacting with RNA-binding proteins, translating deriving pseudogenes. Moreover, associated occurrence progression a variety cancers, new biomarkers for early diagnosis to evaluate curative effects patient prognosis. Here, this paper briefly describes characteristics circRNAs, it further concludes relationship between human cancer. Based on potential encoded family can be divided into two categories, coding RNAs; long RNA, riRNA, tRNA, nsRNA, microRNA (miRNA). In recent years, research has made great progress identification RNAs, which involved biological processes.1Wilusz J.E. Sharp P.A. Molecular biology. A circuitous route RNA.Science. 2013; 340: 440-441Crossref PubMed Scopus (384) Google Scholar, 2Zhao W. Ma X. Liu L. Chen Q. Z. Zhang S. Wang Li H. Wu J. SNHG20: vital lncRNA multiple cancers.J. Cell. Physiol. 2019; (Published online January 15, 2019)https://doi.org/10.1002/jcp.28143Crossref (47) Scholar have nearly 30 years history. They special class derived from back-splicing or exon skipping pre-mRNAs. Unlike do not 5-cap 3-poly(A) tails, produced by exons, downstream 3-splicing donor is connected reverse bond upstream 5-split acceptor.3Pieler T. Theunissen O. TFIIIA: nine fingers--three hands?.Trends Biochem. Sci. 1993; 18: 226-230Abstract Full Text PDF (39) due circular structure, they easily degraded exonucleases, thus having longer half-life. considered inert by-products abnormally spliced RNAs. With emergence high-throughput sequencing, an increasing number been found cells. Increasing evidence shows expression profiles carcinoid tissues different those normal tissues.4Shi P. Sun He B. Song Kong Xue Profiles differentially expressed esophageal breast cancer.Cancer Manag. Res. 2018; 10: 2207-2221Crossref (35) 5Cheng X.Y. Shen [Circular Lung Cancer Research: Biogenesis, Functions Roles].Zhongguo Fei Ai Za Zhi. 21: 50-56PubMed addition, reported participate cellular cancer-related physiological processes, including cancer initiation, progression, metastasis.6Qu Yang Gao Y. Shang R. Dou K. RNA: star RNAs.Cancer Lett. 2015; 365: 141-148Crossref (1222) Therefore, in-depth analysis should help clarify epigenetic level mechanisms. According differences genome constituent sequences, three categories: exon-derived intron-derived composed exons introns.7Ashwal-Fluss Meyer M. Pamudurti N.R. Ivanov A. Bartok Hanan Evantal N. Memczak Rajewsky Kadener circRNA biogenesis competes pre-mRNA splicing.Mol. 2014; 56: 55-66Abstract (1951) 8Kelly Greenman C. Cook P.R. Papantonis Exon Skipping Is Correlated Circularization.J. Mol. Biol. 427: 2414-2417Crossref (245) 9Chen I. C.Y. Chuang T.J. identification, function exonic RNAs.Wiley Interdiscip. Rev. RNA. 6: 563-579Crossref (281) Three models used illuminate possible formation circRNAs: lariat-driven circularization, intron pairing-driven protein-driven circularization (Figure 1). During (cassette-on), lariat still reserves skipped exon(s). circle when splicing occurs before decomposed debranching enzymes. Lariat-driven also known exon-skipping mechanism. The partially folds during causing 5′ site (donor site) approach attack 3′ (receptor intron, whereby formed folded region, while remaining form mRNA.10Jeck W.R. Sorrentino J.A. Slevin M.K. Burd C.E. Marzluff W.F. Sharpless N.E. abundant, conserved, ALU repeats.RNA. 19: 141-157Crossref (2826) 11Wilusz 360° view RNAs: From functions.Wiley 9: e1478Crossref (300) This mechanism most circRNAs. For example, Kelly et al.8Kelly umbilical vein endothelial cells stimulated tumor necrosis factor α growth β contained large circularization. Intron direct Reverse complementary sequences flanks introns mediate Flanking (especially Alu sequences) play crucial part perfectly matched promote circRNAs.12Rybak-Wolf Stottmeister Glažar Jens Pino Giusti Behm Ashwal-Fluss al.Circular Mammalian Brain Are Highly Abundant, Conserved, Dynamically Expressed.Mol. 58: 870-885Abstract (1484) 13Koh Pan Gawad Fan H.C. Kerchner G.A. Wyss-Coray Blumenfeld Y.J. El-Sayed Y.Y. Quake S.R. Noninvasive vivo monitoring tissue-specific global gene humans.Proc. Natl. Acad. USA. 111: 7361-7366Crossref (200) procedure, patterns according whether partial retained, namely, (EcircRNAs) coexist (EIciRNAs).14Bahn J.H. F. Chan T.M. Lin Kim Wong D.T. Xiao landscape microRNA, Piwi-interacting saliva.Clin. Chem. 61: 221-230Crossref (489) Hsa-circ-POLR2A typical circRNA.13Koh proteins (RBPs) shorten distance receptor binding flanks, promoting exons. Muscleblind protein quaking RBPs circMbl circQKI, respectively.15Lasda E. Parker diversity function.RNA. 20: 1829-1842Crossref (848) 16Ivanov Wyler Torti Porath H.T. Orejuela M.R. Piechotta Levanon E.Y. Landthaler Dieterich Analysis reveals hallmarks animals.Cell Rep. 170-177Abstract (673) role some There hypotheses first hypothesis crosses enzyme then cleaves at both ends crossed exon, (lariat);7Ashwal-Fluss therefore, generated splicing. single Another that, base-paired, exon's end tail head, spliceosome bound receptor, resulting introns, cyclized released circRNA.8Kelly Many EcircRNAs contain encode normally standard sites through copolymer Genome-wide sequencing (RNA-seq) data suggests abundant mammalian transcriptome, EcircRNA conserved evolutionary variation, revealing functions.10Jeck 12Rybak-Wolf 17Wilusz Unexpected outputs many protein-coding genes.RNA 2017; 14: 1007-1017Crossref (79) Specifically, indicated steady plasma13Koh saliva,14Bahn suggesting may diagnostic biomarkers. contrast EcircRNAs, (IciRNAs) 3′∼5′ head-to-tail junction regions differ stability, subcellular localization, abundance, preservation, function. IciRNAs circularized chain branchpoints 2′∼5′, degenerating branchpoint avoiding detachment degradation specific way; actually stabilized lariats.15Lasda synthesis requires important site: c-rich containing 11 nt near terminus, length 7 nt, base-rich GU RNA-splicing branch site.16Ivanov Approximately 20% EIciRNAs retain retention would make subclass unique retaining IciRNAs. Mainly located nucleus, interact U1 small nuclear ribonucleoprotein particle (snRNP) transcription parental genes. regulation expression, enhance genes cis emphasize transcriptional strategy RNA-RNA interaction (snRNA).17Wilusz 18Li Huang Bao Zhong G. Yu Hu Dai al.Exon-intron regulate nucleus.Nat. Struct. 22: 256-264Crossref (1852) closed highly resistant digestion; preliminarily purified identified following molecular biology methods.19Jeck Detecting characterizing RNAs.Nat. Biotechnol. 32: 453-461Crossref (1745) (1) Most exonuclease R, niacin phosphatase 5′-terminal exonuclease, retained. Then, circRNA-specific primers quantitative samples, determine quantify after treatment.19Jeck 20Suzuki Zuo M.Q. Malhotra Mayeda Characterization RNase R-digested source consists splicing.Nucleic Acids 2006; 34: e63Crossref (428) (2) no polar end, migration rate cross-linked gel slower Compared homologous nucleic acids fewer weakly gels slower. northern blot analysis.21Tabak H.F. Van der Horst Smit Winter A.J. Mul Groot Koerkamp M.J. Discrimination circles, interlocked circles lariats using two-dimensional polyacrylamide electrophoresis.Nucleic 1988; 16: 6597-6605Crossref (33) 22Suzuki Tsukahara R RNAs.Int. 15: 9331-9342Crossref (314) (3) Fluorescence situ hybridization localize level, interfering (siRNAs) antisense oligonucleotides interfere verify circRNAs.23Li al.Corrigendum: Exon-intron 24: 194Crossref (60) 24Zhang X.O. Xiang J.F. Yin Q.F. Xing Y.H. Zhu L.L. intronic RNAs.Mol. 51: 792-806Abstract (1529) traditional methods, combination bioinformatics provides shortcut discovery low abundance. back-splicing, RNA-seq algorithm extremely inefficient distinguishing structures. Researchers effectively improved strategies algorithms follows: assuming forms rearrangement, candidate sequence boundary was constructed compared data;25Salzman R.E. Olsen M.N. P.L. Brown P.O. Cell-type features expression.PLoS Genet. e1003777Crossref (1391) directly alignment algorithms; detected cDNA designing splice sequences.26Hoffmann Otto Doose Tanzer Langenberger D. Christ Kunz Holdt L.M. Teupser Hackermüller Stadler P.F. multi-split mapping splicing, trans-splicing fusion detection.Genome R34Crossref (180) At present, map-splice,27Li Diao Long non-coding HOXD-AS1 cancer.Clin. Chim. Acta. 487: 197-201Crossref (36) Circ Seq,10Jeck CIRI,28Gao Zhao CIRI: efficient unbiased de novo identification.Genome 4Crossref (670) explorer.29Zhang H.B. Lu Complementary sequence-mediated circularization.Cell. 159: 134-147Abstract CIRI annotation-related only detect transcribed intergenomic but applied annotated unannotated eukaryotes. Since lack poly(A) common oligomeric dT enrichment method ineffective. Ribo-Zero kit, eliminate rRNA remove enrich circRNAs.20Suzuki miRNAs sponges, selective RBPs, pseudogenes, transporting substances information. presented Figure 2. response element (MRE) binds prevents them target mRNAs.30Memczak Elefsinioti Krueger Rybak Maier Mackowiak S.D. Gregersen L.H. Munschauer animal regulatory potency.Nature. 495: 333-338Crossref (5161) 31Hansen T.B. Jensen T.I. Clausen B.H. Bramsen J.B. Finsen Damgaard C.K. Kjems Natural sponges.Nature. 384-388Crossref (5173) proof sponges cerebellar degeneration-related 1 (CDR1as) determined related its functions. CDR1as reduce brain volume hinder development fetal process zebrafish embryos, injection miR-7 restore development, indicating bind miR-7.31Hansen circHIPK3 2 HIPK3 silenced mRNA significantly inhibited Through luciferase screening, 9 18 specifically miR-124 inhibit activity. However, showed miRNA-binding necessarily strong spongy effect, other confirmed viewpoint.32Guo J.U. Agarwal V. Guo Bartel D.P. Expanded characterization RNAs.Genome 409Crossref (1134) 33You Vlatkovic Babic Will Epstein Tushev Akbalik Glock Quedenau al.Neural synaptic regulated plasticity.Nat. Neurosci. 603-610Crossref (743) act phenomenon remains explained. variable transcription. Variable pre-mRNAs isomers methods (different selected), circMBL, second MBL (muscleblind), pre-mRNA. side MBL-binding sites, strongly MBL. obviously influences cyclization circMbl, based flanks.6Qu 7Ashwal-Fluss translation initiation potentially compete host splices. mode balance levels mRNAs. production posttranscriptional level. c-sirt7 pol complex, leading decreased anchor repeat domain-52 deacetylase-7. EIciRNAs, mostly localized ribosome snRNP genes.18Li like perform functions.34Yin Y.W. Carmichael G.G. snoRNA ends.Mol. 2012; 48: 219-230Abstract (306) 35Li Fox A.H. SPArking Interest Noncoding World: New Class SnoRNA-Stabilized LncRNA Influences Alternative Splicing.Mol. 2016; 64: 435-437Abstract (6) When combined complexes, store them,7Ashwal-Fluss complexes. stably molecules As scaffold DNA provide platform DNA. action Ago2 hydrolysis.36Hansen Wiklund E.D. Villadsen S.B. Statham A.L. Clark S.J. miRNA-dependent silencing involving Ago2-mediated cleavage RNA.EMBO 2011; 30: 4414-4422Crossref (702) Du al.37Du W.W. Dhaliwal B.B. Foxo3 retards cell cycle via forming ternary complexes p21 CDK2.Nucleic 44: 2846-2858Crossref (1079) circ-foxo3 cyclin-dependent kinase (CDK2) inhibitor p21. Abdelmohsen al.38Abdelmohsen Panda A.C. Munk Grammatikakis Dudekula D.B. De Noh K.M. Martindale J.L. Gorospe Identification HuR uncovers suppression PABPN1 CircPABPN1.RNA 361-369Crossref (508) circ-PABPN1 could competitively RBP poly(A)-binding (PABPN1) mRNA, reducing mRNA. plays major cancer, proliferation one main By studying better understood, clues provided study tumorigenesis. species basically proteins. if internal entry point (IRES) inserted start codon functionally transcripts. previously shown vitro, engineered IRES, 40S subunit, IRES translation.39Wang Efficient backsplicing produces translatable mRNAs.RNA. 172-179Crossref (460) 40Thomas L.F. Sætrom depleted polymorphisms sites.Bioinformatics. 2243-2246Crossref (148) Similarly, Escherichia coli, open reading frames GFP transfected express GFP.39Wang al.41Du Yong Awan F.M. Identifying Characterizing circRNA-Protein Interaction.Theranostics. 7: 4183-4191Crossref (380) proved time modified m6A; is, methyl group added sixth base molecule, translation. Zhou al.42Zhou Molinie Daneshvar Pondick J.V. Wittenberghe Giallourakis C.C. Mullen Genome-Wide Maps m6A Identify Widespread Cell-Type-Specific Methylation Patterns Distinct mRNAs.Cell 2262-2276Abstract (249) modification specificity. Legnini al.43Legnini Di Timoteo Rossi Morlando Briganti Sthandier Fatica Santini Andronache Wade al.Circ-ZNF609 Can Be Translated Myogenesis.Mol. 66: 22-37.e9Abstract (1313) circ-ZNF609 muscle translate al.44Yang Yan al.Novel Role FBXW7 Repressing Glioma Tumorigenesis.J. Inst. 110: 304-315Crossref (681) circ-FBXW7 inhibits glioma, significance understanding glioma. Studies th

Language: Английский

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Epigenetic Regulation of m6A Modifications in Human Cancer

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 19, P. 405 - 412

Published: Nov. 29, 2019

N6-methyladenosine (m6A) is the most prevalent internal RNA modification, especially within eukaryotic messenger RNAs (mRNAs). m6A modifications of regulate splicing, translocation, stability, and translation into proteins. are catalyzed by methyltransferases, such as METTL3, METTL14, WTAP (writers); removed demethylases fat mass obesity-associated protein (FTO) ALKBH5 (ALKB homolog 5) (erasers); recognized m6A-binding proteins, YTHDF domain-containing proteins IGF2BPs (readers). Abnormal changes in levels these genes closely related to tumor occurrence development. In this paper, we review role human cancer summarize its prospective applications cancer.

Language: Английский

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N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2

Gene, Journal Year: 2019, Volume and Issue: 722, P. 144076 - 144076

Published: Aug. 24, 2019

Language: Английский

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Splicing factor derived circular RNA circUHRF1 accelerates oral squamous cell carcinoma tumorigenesis via feedback loop

Cell Death and Differentiation, Journal Year: 2019, Volume and Issue: 27(3), P. 919 - 933

Published: Sept. 30, 2019

Language: Английский

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METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m6A Modification

Molecular Therapy — Nucleic Acids, Journal Year: 2020, Volume and Issue: 20, P. 1 - 12

Published: Feb. 5, 2020

N6-Methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on N6 nitrogen adenosine. However, roles m6A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate function and mechanism methyltransferase-like 3 (METTL3) OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated tissue samples correlated with poor prognosis patients. Functionally, loss gain studies illustrated promoted proliferation, invasion, migration cells vitro, knockdown inhibited tumor growth vivo. Mechanistically, methylated immunoprecipitation sequencing (MeRIP-seq) targeted 3′ UTR (near to stop codon) c-Myc transcript install modification, thereby enhancing its stability. Furthermore, results revealed YTH N6-methyladenosine binding protein 1 (YTH domain family, member [YTHDF1]) mediated m6A-increased stability mRNA catalyzed by METTL3. In conclusion, our findings herein identify accelerates via YTHDF1-mediated giving rise

Language: Английский

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An Emerging Class of Long Non-coding RNA With Oncogenic Role Arises From the snoRNA Host Genes

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: April 7, 2020

The small nucleolar RNA host geness (SNHG) consist of a group long non-coding RNAs, which are reported in many studies as being overexpressed various cancers. With very few exceptions, the SNHGs (SNHG1, SNHG3, SNHG5, SNHG6, SNHG7, SNHG12, SNHG15, SNHG16, SNHG20) recognized inducing increased proliferation, cell cycle progression, invasion and metastasis cancer cells makes this class transcripts viable biomarker for development aggressiveness. Through our literature research , we also found silencing through interfering RNAs or short hairpin is effective both vitro vivo experiments by lowering solid cancers knock down SNHG new therapeutic option should be investigated more future.

Language: Английский

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Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D1 Pathway

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 16, P. 434 - 441

Published: April 6, 2019

Language: Английский

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Epigenetic Modifications in Head and Neck Cancer

Biochemical Genetics, Journal Year: 2019, Volume and Issue: 58(2), P. 213 - 244

Published: Nov. 11, 2019

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common human malignancy in world, with high mortality poor prognosis for patients. Among risk factors are tobacco alcohol intake, papilloma virus, also genetic epigenetic modifications. Many studies show that events play an important role HNSCC development progression, including DNA methylation, chromatin remodeling, histone posttranslational covalent modifications, effects of non-coding RNA. Epigenetic modifications may influence silencing tumor suppressor genes by promoter hypermethylation, regulate transcription microRNAs changes structure, or induce genome instability through hypomethylation. Moreover, getting to better understand aberrant patterns methylation provide biomarkers early detection diagnosis, while knowledge about target improve therapy extend overall survival. The aim this review present recent which demonstrate regulation HNSCC.

Language: Английский

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Circular RNA circSLC26A4 Accelerates Cervical Cancer Progression via miR-1287-5p/HOXA7 Axis

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 19, P. 413 - 420

Published: Dec. 6, 2019

Circular RNAs (circRNAs) are group of noncoding derived from back-splicing events. Accumulating evidence certifies the critical roles circRNAs in human tumorigenesis. However, role and biogenesis cervical cancer still unclear. Here, a novel identified circRNA, circSLC26A4, was found to be upregulated tissue cells. Clinically, high expression circSLC26A4 related poor survival patients. Functionally, cellular experiments indicated that knockdown repressed proliferation, invasion, tumor growth vitro vivo. Furthermore, acted as sponge miR-1287-5p; moreover, miR-1287-5p targeted 3′ UTR HOXA7 mRNA. Mechanistically, RNA binding protein (RBP) quaking (QKI) interact with QKI response elements (QREs) SLC26A4 gene introns, thereby promoting biogenesis. In conclusion, these findings demonstrate facilitates progression through QKI/circSLC26A4/miR-1287-5p/HOXA7 axis, which might bring therapeutic strategies for cancer.

Language: Английский

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