DOCSLIB.ORG

Mechanism of Lncrna FEZF1-AS1 in Promoting the Occurrence and Development of Oral Squamous Cell Carcinoma Through Targeting Mir-196A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mechanism of Lncrna FEZF1-AS1 in Promoting the Occurrence and Development of Oral Squamous Cell Carcinoma Through Targeting Mir-196A European Review for Medical and Pharmacological Sciences 2019; 23: 6505-6515 Mechanism of lncRNA FEZF1-AS1 in promoting the occurrence and development of oral squamous cell carcinoma through targeting miR-196a L. XU, T.-J. HOU, P. YANG Department of Stomatology, Liaocheng People’s Hospital, Liaocheng, China Lin Xu and Tiejun Hou contributed equally to this work Abstract. – OBJECTIVE: Previous studies have Meanwhile, the miR-196a expression was nega- demonstrated that long non-coding ribonucleic tively correlated with FEZF1-AS1. Subsequent acid (lncRNA) FEZF1-AS1 acts as a cancer-pro- Luciferase reporter gene assay confirmed that moting gene. However, no reports have investi- overexpression of miR-196a could markedly re- gated the role of FEZF1-AS1 in oral squamous cell duce the activity of Luciferase containing wild- carcinoma (OSCC) yet. Therefore, the aim of this type FEZF1-AS1 vector rather than decrease the study was to explore whether FEZF1-AS1 promot- activity of Luciferase containing mutant-type ed the expression characteristics of OSCC by tar- vector or empty vector. These findings further geting miR-196a and to further elucidate the un- indicated that FEZF1-AS1 could be targeted by derlying mechanism of FEZF1-AS1 in promoting miR-196a through this binding site. In addition, the metastasis of OSCC. recovery assay demonstrates that there was a PATIENTS AND METHODS: The expression mutual regulatory effect between FEZF1-AS1 levels of FEZF1-AS1 and miR-196a in 42 pairs of and miR-196a, jointly affecting the malignant OSCC tissues and para-carcinoma tissues were progression of OSCC. detected via quantitative Real Time-Polymerase CONCLUSIONS: The expression of lncRNA Chain Reaction (qRT-PCR). The correlation FEZF1-AS1 was markedly up-regulated in OSCC, of FEZF1-AS1 expression with clinical indexes which was significantly correlated with patho- and prognosis of OSCC patients was analyzed. logical stage and poor prognosis of OSCC pa- Moreover, the expression levels of FEZF1-AS1 tients. Therefore, it was believed that FEZF1- and miR-196a in OSCC cells were detected via AS1 might promote the malignant progression qRT-PCR. FEZF1-AS1 knockdown and miR-196a of OSCC by regulating miR-196a. over-expression models were established using Key Words: lentivirus transfection in OSCC cell lines (CAL- LncRNA FEZF1-AS1, MiR-196a, Oral squamous cell 27 and Tca8113). Subsequently, the influences carcinoma (OSCC), Proliferation. of FEZF1-AS1 and miR-196a on the biological functions of OSCC cells were analyzed via Cell Counting Kit-8 (CCK-8) assay, colony formation assay and 5-Ethynyl-2’-deoxyuridine (EdU) assay, respectively. Furthermore, the potential mecha- Introduction nism was explored using the Luciferase reporter gene and recovery assays. The oral cavity is located at the initial position RESULTS: The results of qRT-PCR proved of the digestive and respiratory tract, which pos- that the expression level of FEZF1-AS1 in OSCC sesses important physiological functions1,2. Oral tissues was significantly higher than that of cancer is considered one of the top ten frequently- para-carcinoma tissues, and the difference was statistically significant. The pathological stage occurring cancers in the body. It can cause dys- was significantly higher in patients with high- functions of eating, speech and respiratory in se- expression FEZF1-AS1 than those with low-ex- vere cases, seriously affecting the quality of life of pression FEZF1-AS1, while the overall survival patients1,2. Squamous cell carcinoma is the most rate was remarkably lower. The proliferation common type of oral cancer, accounting for more ability of cells in FEZF1-AS1 silencing group de- than 90% of oral cancer patients. The prognosis of clined significantly when compared with the NC squamous cell carcinoma is relatively poor, with a group. Similarly, qRT-PCR results verified that 3-5 the expression of miR-196a in OSCC cell lines 5-year survival rate of 50-60% only . Oral squa- and tissues was significantly reduced as well. mous cell carcinoma (OSCC) is generally derived Corresponding Author: Tiejun Hou, MM; e-mail: [email protected] 6505 L. Xu, T.-J. Hou, P. Yang from oral mucosal epithelium. Due to the reasons ment of tumors. Therefore, the aim of this study that the oral cavity is located at the key position was to investigate the mechanism of lncRNA of the digestive and respiratory tract and there are FEZF1-AS1 in affecting clinical parameters, many important organs, postoperative recurrence prognosis and malignant progression of OSCC and cervical lymph node metastasis of OSCC oc- by absorbing miR-196a. cur easily6,7. In recent years, synthetic serial ther- apy based on surgery has been widely applied in the diagnosis and treatment of OSCC. Meanwhile, the importance of radical and complete treatment Patients and Methods in the prognosis of patients has been emphasized. However, the 5-year survival rate of patients with Patients and OSCC Specimens advanced tumor and recurrence remains far from A total of 42 paired OSCC tissues and para- satisfactory despite various treatment methods8-10. carcinoma tissues were collected. All specimens Therefore, the study of the pathogenesis of OSCC, were obtained from tissues subjected to operation especially the detection and diagnosis of specific and needle biopsy or bronchoscopic biopsy in the early tumor markers, has been increasingly more Oncology Department and Stomatology Depart- important8,10. ment. In addition, no patient underwent anti- Previous molecular biological studies11,12 on tumor therapies such as radiotherapy and che- tumors have mainly focused on genes that can motherapy before the operation. This study was encode proteins. However, non-coding genes are approved by the Ethics Committee of Liaocheng ignored. Non-coding genes are a general term People’s Hospital. Informed consent was obtained for genes with no protein-encoding functions, from each subject before the study. All patients and their transcription products are non-coding were followed up via telephone and clinic after ribonucleic acid (ncRNA)13,14. There are many discharge. Follow-up information was collected, members of the ncRNA family, of which micro including general conditions, clinical symptoms RNA (miRNA) and long ncRNA (lncRNA) are and imaging examinations. the most notable15,16. Currently, molecular biologi- cal mechanism of miRNA has been studied. It has Cell Lines and Reagents been found that miRNA can silence mRNA at the Four human OSCC cell lines (Fadu, SCC-25, post-transcriptional level through complementary CAL-27, and Tca8113) and one normal human base pairing. The correlations of miRNA with oral cell line (Hs 680.Tg) were purchased from the pathogenesis of malignancies and diagnostic the American Type Culture Collection (ATCC; values have been confirmed as well17,18. LncRNAs Manassas, VA, USA). Dulbecco’s Modified Ea- are a kind of RNA molecules with more than 200 gle’s Medium (DMEM) and fetal bovine serum nt in length, with no protein-encoding ability. (FBS) were purchased from Life Technologies Previous studies19-21 have indicated that they ex- (Gaithersburg, MD, USA). All cells were cultured ert biological functions in the form of RNA. Ln- in DMEM containing 10% FBS in an incubator cRNA was regarded as “noise” produced in the with 5% CO2 at 37°C. gene transcription process in the past. However, increasingly more evidence has suggested that ln- Cell Transfection cRNAs are involved in regulating gene expression Control group (NC) and FEZF1-AS1 silencing at epigenetic, transcriptional and post-transcrip- group containing FEZF1-AS1 lentiviral sequence tional levels. Moreover, lncRNAs play extensive (sh-FEZF1-AS1), and control group (miR-NC) and important roles in life processes, such as cell and overexpression group containing miRNA- differentiation, cell fate determination, prolifera- 196a lentiviral sequence (miRNA-196a mimics) tion and migration12,21. were purchased from Shanghai GenePharma Co., In the present work, the expressions of Ltd. (Shanghai, China). The cells were first seed- FEZF1-AS1 and miR-196a in 42 pairs of OSCC ed into 6-well plates, followed by culture until tissues and para-carcinoma tissues were ana- cell density reached 70%. Subsequently, the cells lyzed. The influences of FEZF1-AS1 and miR- were transfected with lentivirus according to the 196a on the biological functions of OSCC cells manufacturer’s instructions. 48 h after transfec- were explored as well. Previous studies have tion, the cells were collected for quantitative Real pointed out that FEZF1-AS1 and miR-196a play Time-Polymerase Chain Reaction (qRT-PCR) important roles in the occurrence and develop- analysis and functional cell assays. 6506 LncRNA FEZF1-AS1 and oral squamous cell carcinoma Cell Proliferation Assay was used for amplification, including 2×SYBR 48 h after transfection, the cells were collected Green PCR Master Mix (Thermo Fisher Scientific, and seeded into 96-well plates (2000 cells/well). Waltham, MA, USA), an appropriate amount of After culturing for 6 h, 24 h, 48 h, and 72 h, the cDNA as a template and primers (0.4 mol/L). Three cells were added with Cell Counting Kit-8 (CCK- replicates were set for each sample. The correspond- 8) reagent (Dojindo Laboratories, Kumamoto, Ja- ing forward and reverse primers were designed and pan), respectively. After incubation for another 2 synthesized according to target genes. PCR ampli- h in the dark, the optical density (OD) value of fication was conducted on a qPCR instrument, with each well at the wavelength of 490 nm was mea- β-actin as an internal reference. The expression level sured using a microplate reader. Finally, experi- of the genes was calculated by the RQ=2-ΔΔCt meth- mental data were analyzed. od. This experiment was repeated three times Primers used in this study were as follows: Colony Formation Assay FEZF1-AS1: forward: 5’-TCGCTCAATG- 48 h after transfection the cells were collected, GAGTGACGGCA-3’, reverse: 5’-CGGCT- and 200 cells were inoculated into each well of GAGACCGCTGAGAACTT-3’.
Load more

Recommended publications
  • Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production
    The Journal of Neuroscience, March 25, 2015 • 35(12):4903–4916 • 4903 Development/Plasticity/Repair Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production Melody P. Lun,1,3 XMatthew B. Johnson,2 Kevin G. Broadbelt,1 Momoko Watanabe,4 Young-jin Kang,4 Kevin F. Chau,1 Mark W. Springel,1 Alexandra Malesz,1 Andre´ M.M. Sousa,5 XMihovil Pletikos,5 XTais Adelita,1,6 Monica L. Calicchio,1 Yong Zhang,7 Michael J. Holtzman,7 Hart G.W. Lidov,1 XNenad Sestan,5 Hanno Steen,1 XEdwin S. Monuki,4 and Maria K. Lehtinen1 1Department of Pathology, and 2Division of Genetics, Boston Children’s Hospital, Boston, Massachusetts 02115, 3Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, 4Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine, California 92697, 5Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, 6Department of Biochemistry, Federal University of Sa˜o Paulo, Sa˜o Paulo 04039, Brazil, and 7Pulmonary and Critical Care Medicine, Department of Medicine, Washington University, St Louis, Missouri 63110 A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) choroid plexus. We find that positional identitiesofmouse,macaque,andhumanchoroidplexiderivefromgeneexpressiondomainsthatparalleltheiraxialtissuesoforigin.We thenshowthatmolecularheterogeneitybetweentelencephalicandhindbrainchoroidplexicontributestoregion-specific,age-dependent protein secretion in vitro.
    [Show full text]
  • Epigenetic Mechanisms of Lncrnas Binding to Protein in Carcinogenesis
    cancers Review Epigenetic Mechanisms of LncRNAs Binding to Protein in Carcinogenesis Tae-Jin Shin, Kang-Hoon Lee and Je-Yoel Cho * Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea; [email protected] (T.-J.S.); [email protected] (K.-H.L.) * Correspondence: [email protected]; Tel.: +82-02-800-1268 Received: 21 September 2020; Accepted: 9 October 2020; Published: 11 October 2020 Simple Summary: The functional analysis of lncRNA, which has recently been investigated in various fields of biological research, is critical to understanding the delicate control of cells and the occurrence of diseases. The interaction between proteins and lncRNA, which has been found to be a major mechanism, has been reported to play an important role in cancer development and progress. This review thus organized the lncRNAs and related proteins involved in the cancer process, from carcinogenesis to metastasis and resistance to chemotherapy, to better understand cancer and to further develop new treatments for it. This will provide a new perspective on clinical cancer diagnosis, prognosis, and treatment. Abstract: Epigenetic dysregulation is an important feature for cancer initiation and progression. Long non-coding RNAs (lncRNAs) are transcripts that stably present as RNA forms with no translated protein and have lengths larger than 200 nucleotides. LncRNA can epigenetically regulate either oncogenes or tumor suppressor genes. Nowadays, the combined research of lncRNA plus protein analysis is gaining more attention. LncRNA controls gene expression directly by binding to transcription factors of target genes and indirectly by complexing with other proteins to bind to target proteins and cause protein degradation, reduced protein stability, or interference with the binding of other proteins.
    [Show full text]
  • Transcription Factors from Multiple Families Ensure Enhancer Selectivity
    bioRxiv preprint doi: https://doi.org/10.1101/2020.09.04.283036; this version posted September 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Transcription factors from multiple families ensure enhancer selectivity and robust neuron terminal differentiation Angela Jimeno-Martín, Erick Sousa, Noemi Daroqui, Rebeca Brocal-Ruiz, Miren Maicas, Nuria Flames* Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV- CSIC, Valencia, 46010, Spain * Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.04.283036; this version posted September 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 SUMMARY 2 To search for general principles underlying neuronal regulatory programs we 3 built an RNA interference library against all transcription factors (TFs) encoded 4 in C. elegans genome and systematically screened for specification defects in 5 ten different neuron types of the monoaminergic (MA) superclass. 6 We identified over 90 TFs involved in MA specification, with at least ten different 7 TFs controlling differentiation of each individual neuron type. These TFs belong 8 predominantly to five TF families (HD, bHLH, ZF, bZIP and NHR). Next, 9 focusing on the complexity of terminal differentiation, we identified and 10 functionally characterized the dopaminergic terminal regulatory program. We 11 found that seven TFs from four different families act in a TF collective to provide 12 genetic robustness and to impose a specific gene regulatory signature enriched 13 in the regulatory regions of dopamine effector genes.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • Genomics of Mature and Immature Olfactory Sensory Neurons Melissa D
    University of Kentucky UKnowledge Physiology Faculty Publications Physiology 8-15-2012 Genomics of Mature and Immature Olfactory Sensory Neurons Melissa D. Nickell University of Kentucky, [email protected] Patrick Breheny University of Kentucky, [email protected] Arnold J. Stromberg University of Kentucky, [email protected] Timothy S. McClintock University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/physiology_facpub Part of the Genomics Commons, and the Physiology Commons Repository Citation Nickell, Melissa D.; Breheny, Patrick; Stromberg, Arnold J.; and McClintock, Timothy S., "Genomics of Mature and Immature Olfactory Sensory Neurons" (2012). Physiology Faculty Publications. 66. https://uknowledge.uky.edu/physiology_facpub/66 This Article is brought to you for free and open access by the Physiology at UKnowledge. It has been accepted for inclusion in Physiology Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Genomics of Mature and Immature Olfactory Sensory Neurons Notes/Citation Information Published in Journal of Comparative Neurology, v. 520, issue 12, p. 2608-2629. Copyright © 2012 Wiley Periodicals, Inc. This is the peer reviewed version of the following article: Nickell, M. D., Breheny, P., Stromberg, A. J., and McClintock, T. S. (2012). Genomics of mature and immature olfactory sensory neurons. Journal of Comparative Neurology, 520: 2608–2629, which has been published in final form at http://dx.doi.org/ 10.1002/cne.23052. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
    [Show full text]
  • High-Density SNP Association Study and Copy Number Variation Analysis of the AUTS1 and AUTS5 Loci Implicate the IMMP2L–DOCK4 Gene Region in Autism Susceptibility
    Molecular Psychiatry (2010) 15, 954–968 & 2010 Macmillan Publishers Limited All rights reserved 1359-4184/10 www.nature.com/mp ORIGINAL ARTICLE High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L–DOCK4 gene region in autism susceptibility E Maestrini1,11, AT Pagnamenta2,11, JA Lamb2,3,11, E Bacchelli1, NH Sykes2, I Sousa2, C Toma1, G Barnby2, H Butler2, L Winchester2, TS Scerri2, F Minopoli1, J Reichert4, G Cai4, JD Buxbaum4, O Korvatska5, GD Schellenberg6, G Dawson7,8, A de Bildt9, RB Minderaa9, EJ Mulder9, AP Morris2, AJ Bailey10 and AP Monaco2, IMGSAC12 1Department of Biology, University of Bologna, Bologna, Italy; 2The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; 3Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK; 4Department of Psychiatry, Seaver Autism Research Center, Mount Sinai School of Medicine, New York, NY, USA; 5Geriatric Research Education and Clinical Centre, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA, USA; 6Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 7Autism Speaks, New York, NY, USA; 8Department of Psychology, University of Washington, Seattle, WA, USA; 9Department of Psychiatry, Child and Adolescent Psychiatry, University Medical Center Groningen, Groningen, The Netherlands and 10University Department of Psychiatry, Warneford Hospital, Oxford, UK Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences.
    [Show full text]
  • Fezf1 and Fezf2 Are Required for Olfactory Development and Sensory Neuron Identity
    RESEARCH ARTICLE Fezf1 and Fezf2 Are Required for Olfactory Development and Sensory Neuron Identity Matthew J. Eckler,1 William L. McKenna,1 Sahar Taghvaei,1 Susan K. McConnell,2 and Bin Chen1* 1Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064 2Department of Biological Sciences, Stanford University, Stanford, California 94305 ABSTRACT finger transcription factors, FEZF1 and FEZF2, regulate The murine olfactory system consists of main and the identity of MOE sensory neurons and are essential accessory systems that perform distinct and overlap- for the survival of VNO neurons respectively. Fezf1 is ping functions. The main olfactory epithelium (MOE) is predominantly expressed in the MOE while Fezf2 expres- primarily involved in the detection of volatile odorants, sion is restricted to the VNO. In Fezf1-deficient mice, while neurons in the vomeronasal organ (VNO), part of olfactory neurons fail to mature and also express markers the accessory olfactory system, are important for phero- of functional VNO neurons. In Fezf2-deficient mice, VNO mone detection. During development, the MOE and VNO neurons degenerate prior to birth. These results identify both originate from the olfactory pit; however, the mech- Fezf1 and Fezf2 as important regulators of olfactory sys- anisms regulating development of these anatomically dis- tem development and sensory neuron identity. J. Comp. tinct organs from a common olfactory primordium are Neurol. 519:1829–1846, 2011. unknown. Here we report that two closely related zinc- VC 2011 Wiley-Liss, Inc. INDEXING TERMS: main olfactory epithelium; vomeronasal organ; olfactory receptor; vomeronasal receptor; cell fate To perceive their chemical environment, mice coordi- tion in the ventromedial wall that produces the VNO (Fig.
    [Show full text]
  • Anterior CNS Expansion Driven by Brain Transcription Factors Jesu´S Rodriguez Curt1†, Behzad Yaghmaeian Salmani1‡, Stefan Thor1,2§*
    RESEARCH ARTICLE Anterior CNS expansion driven by brain transcription factors Jesu´s Rodriguez Curt1†, Behzad Yaghmaeian Salmani1‡, Stefan Thor1,2§* 1Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden; 2School of Biomedical Sciences, University of Queensland, Saint Lucia, Australia Abstract During CNS development, there is prominent expansion of the anterior region, the brain. In Drosophila, anterior CNS expansion emerges from three rostral features: (1) increased progenitor cell generation, (2) extended progenitor cell proliferation, (3) more proliferative daughters. We find that tailless (mouse Nr2E1/Tlx), otp/Rx/hbn (Otp/Arx/Rax) and Doc1/2/3 (Tbx2/ 3/6) are important for brain progenitor generation. These genes, and earmuff (FezF1/2), are also important for subsequent progenitor and/or daughter cell proliferation in the brain. Brain TF co- misexpression can drive brain-profile proliferation in the nerve cord, and can reprogram developing *For correspondence: wing discs into brain neural progenitors. Brain TF expression is promoted by the PRC2 complex, [email protected] acting to keep the brain free of anti-proliferative and repressive action of Hox homeotic genes. † Hence, anterior expansion of the Drosophila CNS is mediated by brain TF driven ‘super-generation’ Present address: Department of Zoology, University of of progenitors, as well as ‘hyper-proliferation’ of progenitor and daughter cells, promoted by Cambridge, Cambridge, United PRC2-mediated repression of Hox activity. Kingdom; ‡Department of Cell DOI: https://doi.org/10.7554/eLife.45274.001 and Molecular Biology, Karolinska Institute, Stockholm, Sweden; §School of Biomedical Sciences, University of Introduction Queensland, Saint Lucia, A striking feature of the central nervous system (CNS) is the significant anterior expansion of the Australia brain relative to the nerve cord.
    [Show full text]
  • Transcriptomic and Open Chromatin Atlas of High-Resolution Anatomical Regions in the Rhesus Macaque Brain
    ARTICLE https://doi.org/10.1038/s41467-020-14368-z OPEN Transcriptomic and open chromatin atlas of high-resolution anatomical regions in the rhesus macaque brain Senlin Yin1,7, Keying Lu1,7, Tao Tan2,3,4,7, Jie Tang 1,7, Jingkuan Wei3, Xu Liu5, Xinlei Hu1, Haisu Wan5, Wei Huang6, Yong Fan4*, Dan Xie 1* & Yang Yu 2* 1234567890():,; The rhesus macaque is a prime model animal in neuroscience. A comprehensive tran- scriptomic and open chromatin atlas of the rhesus macaque brain is key to a deeper understanding of the brain. Here we characterize the transcriptome of 416 brain samples from 52 regions of 8 rhesus macaque brains. We identify gene modules associated with specific brain regions like the cerebral cortex, pituitary, and thalamus. In addition, we discover 9703 novel intergenic transcripts, including 1701 coding transcripts and 2845 lncRNAs. Most of the novel transcripts are only expressed in specific brain regions or cortical regions of specific individuals. We further survey the open chromatin regions in the hippocampal CA1 and several cerebral cortical regions of the rhesus macaque brain using ATAC-seq, revealing CA1- and cortex-specific open chromatin regions. Our results add to the growing body of knowledge regarding the baseline transcriptomic and open chromatin profiles in the brain of the rhesus macaque. 1 Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041 Chengdu, China. 2 Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191 Beijing, China. 3 Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, 650500 Kunming, Yunnan, China.
    [Show full text]
  • Lncrna-FEZF1-AS1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling
    Author Manuscript Published OnlineFirst on June 18, 2018; DOI: 10.1158/1078-0432.CCR-17-2967 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 LncRNA—FEZF1-AS1 promotes tumor proliferation and metastasis in 2 colorectal cancer by regulating PKM2 signaling 3 4 Zehua Bian1†, Jiwei Zhang1†, Min Li1, Yuyang Feng1,2, Xue Wang2, Jia Zhang1,2, Surui Yao1, 5 Guoying Jin1, Jun Du3, Weifeng Han3, Yuan Yin1, Shenglin Huang4, Bojian Fei3, Jian Zou5*, 6 Zhaohui Huang1,2* 7 8 1 Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, 9 China. 10 2 Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 11 214122, China. 12 3 Department of Surgical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 13 214062, China. 14 4 Institutes of Biomedical Sciences and Shanghai Cancer Center, Shanghai Medical College, 15 Fudan University, Shanghai, 200032. China. 16 5 Center of Clincical Research, Wuxi People's Hospital of Nanjing Medical University, Wuxi, 17 Jiangsu, 214023, China. 18 † These authors contributed equally to this work. 19 20 * Correspondence author: Zhaohui Huang, Wuxi Cancer Institute, Affiliated Hospital of 21 Jiangnan University, 200 Huihe Road, Wuxi, 214062, China. Tel/Fax: 86-510-88682087; 22 E-mail: [email protected], [email protected]. Jian Zou, Center of Clincical 23 Research, Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 24 214023, China. Tel: 86-510-85350368; E-mail: [email protected]. 25 26 Running Title: Oncogenic function of FEZF1-AS1 in colorectal cancer 27 28 Keywords: Long non-coding RNA, FEZF1-AS1, Colorectal cancer, PKM2, STAT3 29 Downloaded from clincancerres.aacrjournals.org on September 30, 2021.
    [Show full text]
  • Mechanisms and Functions of Long Non-Coding Rnas at Multiple Regulatory Levels
    International Journal of Molecular Sciences Review Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels Xiaopei Zhang 1, Wei Wang 1 , Weidong Zhu 2, Jie Dong 1, Yingying Cheng 1, Zujun Yin 2,* and Fafu Shen 1,* 1 State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, NO. 61 Daizong Street, Tai’an 271018, Shandong, China; [email protected] (X.Z.); [email protected] (W.W.); [email protected] (J.D.); [email protected] (Y.C.) 2 State Key Laboratory of Cotton Biology, Chinese Academy of Agricultural Sciences Cotton Research Institute, Key Laboratory for Cotton Genetic Improvement, Anyang 45500, Henan, China; [email protected] * Correspondence: [email protected] (Z.Y.); [email protected] (F.S.); Tel.: +86-372-256-2219 (Z.Y.); +86-538-824-6011 (F.S.); Fax: +86-372-256-2311 (Z.Y.); +86-538-824-2226 (F.S.) Received: 20 September 2019; Accepted: 6 November 2019; Published: 8 November 2019 Abstract: Long non-coding (lnc) RNAs are non-coding RNAs longer than 200 nt. lncRNAs primarily interact with mRNA, DNA, protein, and miRNA and consequently regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels in a variety of ways. They play important roles in biological processes such as chromatin remodeling, transcriptional activation, transcriptional interference, RNA processing, and mRNA translation. lncRNAs have important functions in plant growth and development; biotic and abiotic stress responses; and in regulation of cell differentiation, the cell cycle, and the occurrence of many diseases in humans and animals.
    [Show full text]
  • SCIENCE CHINA Function of FEZF1 During Early Neural Differentiation Of
    SCIENCE CHINA Life Sciences • RESEARCH PAPER • doi: 10.1007/s11427-017-9155-4 Function of FEZF1 during early neural differentiation of human embryonic stem cells Xin Liu1,2, Pei Su1,2, Lisha Lu1,2, Zicen Feng1,2, Hongtao Wang1,2* & Jiaxi Zhou1,2* 1State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; 2Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin 300000, China Received September 13, 2017; accepted November 19, 2017; published online January 2, 2018 The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1(FEZF1)asa potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs.
    [Show full text]