DOCSLIB.ORG

Microrna-203 Induces Apoptosis by Targeting Bmi-1 in YD-38 Oral

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Microrna-203 Induces Apoptosis by Targeting Bmi-1 in YD-38 Oral ANTICANCER RESEARCH 38 : 3477-3485 (2018) doi:10.21873/anticanres.12618 MicroRNA-203 Induces Apoptosis by Targeting Bmi-1 in YD-38 Oral Cancer Cells JAE-SUNG KIM 1* , DAE WOO CHOI 2* , CHUN SUNG KIM 1, SUN-KYOUNG YU 1, HEUNG-JOONG KIM 1, DAE-SAN GO 1, SEUL AH LEE 1, SUNG MIN MOON 1, SU GWAN KIM 1, HONG SUNG CHUN 3, JEONGSUN KIM 4, JONG-KEUN KIM 2 and DO KYUNG KIM 1 1Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju, Republic of Korea; 2Department of Pharmacology, Chonnam National University Medical School, Gwangju, Republic of Korea; 3Department of Biomedical Science, Chosun University, Gwangju, Republic of Korea; 4Department of Dental Hygiene, Gwangju Health University, Gwangju, Republic of Korea Abstract. Background/Aim: MicroRNAs (miRNAs) are by directly targeting the 3’-untranslated region. Conclusion: closely associated with a number of cellular processes, miR-203 induces apoptosis in YD-38 cells by directly including cell development, differentiation, proliferation, targeting Bmi-1, which suggests its possible application as carcinogenesis, and apoptosis. The aim of the present study an anti-cancer therapeutic. was to elucidate the molecular mechanisms underlying the tumor suppressor activity of miRNA-203 (miR-203) in MicroRNAs (miRNAs) are a group of naturally-occurring, YD-38 human oral cancer cells. Materials and Methods: small (19-25 nucleotides), non-coding RNAs that are Polymerase chain reaction analysis, MTT assay, DNA important post-transcriptional regulators of gene expression fragmentation assay, fluorescence-activated cell-sorting (1). miRNAs function by binding to the 3’-untranslated analysis, gene array, immunoblotting, and luciferase assay region (3’-UTR) of their target genes, and thereby were carried out in YD-38 cells. Results: miR-203 expression inhibiting translation or inducing mRNA degradation (2). was significantly down-regulated in YD-38 cells compared They have been estimated to regulate up to 60% of protein- to expression levels in normal human oral keratinocytes. coding genes (3) and have been shown to control various miR-203 decreased the viability of YD-38 cells in a time- and cellular biological processes, such as cell development, dose-dependent manner. In addition, over-expression of miR- differentiation, proliferation, carcinogenesis, and apoptosis 203 significantly increased not only DNA segmentation, but (4-6). In addition, many studies have demonstrated that also the apoptotic population of YD-38 cells. These results miRNAs function as oncogenes or suppressive genes and indicate that miR-203 overexpression induces apoptosis in that their aberrant expression contributes to various human YD-38 cells. Target gene array analysis revealed that the diseases such as cancer (7). Further investigation of expression of the polycomb complex protein gene Bmi-1, a miRNA involvement in cancer could help us better representative oncogene, was significantly down-regulated understand the molecular mechanisms responsible for by miR-203 in YD-38 cells. Moreover, both mRNA and cancer development and lead to novel strategies for the protein levels of Bmi-1 were significantly reduced in YD-38 effective control of cancer (7, 8). Therefore, current studies cells transfected with miR-203. These results indicate that have focused on the utility of miRNAs as diagnostic and Bmi-1 is a target gene of miR-203. A luciferase reporter prognostic tools and potential therapeutic targets. However, assay confirmed that miR-203 suppressed Bmi-1 expression their biological functions and cellular mechanisms are largely unknown (7, 8). Many studies have examined the role of miRNA-203 (miR- 203 ) as a tumor suppressor in carcinogenesis. Saini et al. *These Authors contributed equally to this study. reported that miR-203 regulates cell progression and metastasis in prostate cancer by targeting a cohort of pro- Correspondence to: Do Kyung Kim, Department of Oral metastatic genes (9). Bo et al. reported that miR-203 Physiology, School of Dentistry, Chosun University, 309 Pilmun- daero, Dong-gu, Gwangju 61452, Republic of Korea. Tel: +82 suppresses bladder cancer progression by repressing the Bcl- 622306893, Fax: +82 622326896, e-mail: [email protected] w expression (10). In another study, Takeshita et al. showed that miR-203 inhibits cell migration and invasion by Key Words: miR-203 , tumor suppressor, oral cancer, Bmi-1 , apoptosis. regulating LASP1 expression in esophageal squamous cell 3477 ANTICANCER RESEARCH 38 : 3477-3485 (2018) carcinoma (11). These studies showed that miR-203 has anti- dissolve the formazan crystals the cells were resuspended in 150 μl tumor activity in several human cancers (9-11). However, the of dimethyl sulfoxide (DMSO), and the optical density at 495 nm anti-tumorigenesis mechanism and signaling pathway (OD 495 ) of the solution was determined using a spectrometer. The experiments were repeated at least three times. underlying the tumor suppressor activity of miR-203 in oral cancers are still unclear. Thus, in the present study, the DNA fragmentation. To evaluate genomic DNA fragmentation as an biological functions and mechanisms of the tumor suppressor apoptotic phenomenon in YD-38 cells treated with miR-203 , a DNA miRNA function of miR-203 were investigated, and results fragmentation assay was performed according to our laboratory showed that miR-203 functions by repressing the activity of method. miR-203 was transfected into cultured YD-38 cells using Bmi-1 in oral cancer cells. Lipofectamine 2000 for 48 h. After transfection, pellets containing 6 Bmi-1 , B-cell-specific Moloney murine leukemia virus 1×10 cells were lysed by incubation in lysis buffer (25 mM EDTA, insertion site 1, is a core member of the polycomb repressive 10 mM Tris-HCL pH 8.0 and 0.5% Triton X-100) for 20 min at 4˚C. After centrifugation at 12,000 × g for 30 min at 4˚C, the supernatant complex 1 (RPC1), RCP1 can modify chromatin structure was mixed with an equal volume of the phenol:chloroform:isoamyl and regulate the transcription of numerous target genes, alcohol (v/v/v, 25:24:1). After centrifugation at 12,000 × g for 30 min including the INK4a/ARF locus, which contains the genes at 4˚C, the DNA was precipitated with sodium acetate and 70% encoding p16 ink4a and p19 arf , two proteins that function to ethanol, and then dried and dissolved in a deionized water-RNase suppress proliferation and promote apoptosis (12, 13). Bmi-1 solution. The purified DNA was then electrophoresed on a 1% was originally identified as an oncogene that cooperates with agarose gel visualized with ethidium bromide. c-Myc during the progression of B-cell lymphoma (14) and Quantitative estimation of apoptosis. Apoptosis was assessed by it is overexpressed in a variety of human cancers, including fluorescence-activated cell-sorting (FACS) using an Annexin V- breast, colon and gastric cancer (15-17). However, the FITC/7-AAD Kit (BD Biosciences, NJ, USA). The cells were mechanism underlying Bmi-1 regulation in cancer cells is resuspended in a binding buffer (BD Biosciences), Annexin V-FITC largely unknown. The aim of the present study was to and 7-amino-actinomycin D (7-AAD) were added, and the mixture determine the biological function of miR-203 as a tumor was incubated in the dark for 15 min. The cells were then suppressor in YD-38 oral cancer cells and the molecular resuspended in 300 μl of binding buffer and analyzed using a mechanism of miR-203- mediated Bmi-1 repression in oral FACSCalibur flow cytometer (Becton-Dickinson, San Jose, CA, USA). Data analysis was performed using Cell Quest software cancer cells. (Becton-Dickinson). Materials and Methods Identification of miR-203 target genes. To determine the miR-203 target genes, we performed a microarray experiment as previously Cell line and cell cultures. Normal human oral keratinocytes described (18). DNA samples isolated from YD-38 cells (NHOKs) were purchased from ScienCell Research Laboratories overexpressing miR-203 were run on a DMET microarray (Carlsbad, CA, USA) and maintained according to the manufacturer’s (Affymetrix, Santa Clara, CA, USA) using the DMET Plus premier instructions. The human oral cancer cell line YD-38 was obtained by pack kit according to the manufacturer’s protocol. the Korean Cell Line Bank (Seoul, Korea) and cultured in RPMI- 1640 (Gibco BRL, Grand Island, NY, USA) supplemented with 10% Quantitative real-time PCR (qRT-PCR) and quantitative PCR (qPCR) . fetal bovine serum (FBS, Atlas Biological, Fort Collins, CO, USA) Total RNA, including mature miRNA, was isolated from cultured cells at 37˚C in an atmosphere containing 5% CO 2. using the miRNeasy mini kit (Qiagen, Germantown, MD, USA), and the RNA was quantified by spectrophotometry (NanoDrop 2000; miRNAs and transfection. miR-203 and scrambled miR-203 mRNA Thermo Fisher Scientific Inc., Waltham, MA, USA) according to the (mimic miR-203 ) were purchased from Ambion (Austin, TX, USA). manufacturer’s instructions. The miRNA was reverse transcribed using The miR-203 , mimic miR-203 , and psiCHECK-2-promoter -Bmi-1 - the miScript Reverse Transcription kit (Qiagen) using 1 μg of total 3’-untranslated region (3’-UTR) were transfected into cultured YD- RNA. The TaqMan miRNA assay kit (Life Technologies, Grand 38 cells using Lipofectamine™ 2000 (Invitrogen, Carlsbad, CA, Island, NY, USA) was used to examine miR-203 (5’- USA) according to the manufacturer’s instructions. The GTGAAATGTTTAGGACCACTAG-3’) expression by qRT-PCR. The experimental cells were incubated with 1 ng/ml miRNA for 2 days. qRT-PCR results, which were recorded as threshold cycle number (Ct), were normalized to glyceraldehyde 3-phosphate dehydrogenase Cell viability assay. The MTT assay was used to assess the effect (GAPDH ) (h GAPDH -F, 5’-CTTTGGTATCGTGGAAGGACTC-3’; of miR-203 on YD-38 oral cancer cell proliferation. The cells were hGAPDH -R, 5’-AGTAGAGGCAGGGATGATGT-3’), which was plated at a density of 5 ×10 3 cells/well in 96-well plates and allowed used as an internal control, and the comparative threshold cycle to attach to the well overnight.
Load more

Recommended publications
  • Nanoliposomal Delivery of Microrna-203 Suppresses Migration of Triple-Negative Breast Cancer Through Distinct Target Suppression
    non-coding RNA Article Nanoliposomal Delivery of MicroRNA-203 Suppresses Migration of Triple-Negative Breast Cancer through Distinct Target Suppression Shuxuan Song 1, Kelsey S. Johnson 1, Henry Lujan 2, Sahar H. Pradhan 2 , Christie M. Sayes 2 and Joseph H. Taube 1,* 1 Department of Biology, Baylor University, Waco, TX 76706, USA; [email protected] (S.S.); [email protected] (K.S.J.) 2 Department of Environmental Science, Baylor University, Waco, TX 76706, USA; [email protected] (H.L.); [email protected] (S.H.P.); [email protected] (C.M.S.) * Correspondence: [email protected] Abstract: Triple-negative breast cancers affect thousands of women in the United States and dis- proportionately drive mortality from breast cancer. MicroRNAs are small, non-coding RNAs that negatively regulate gene expression post-transcriptionally by inhibiting target mRNA translation or by promoting mRNA degradation. We have identified that miRNA-203, silenced by epithelial– mesenchymal transition (EMT), is a tumor suppressor and can promote differentiation of breast cancer stem cells. In this study, we tested the ability of liposomal delivery of miR-203 to reverse aspects of breast cancer pathogenesis using breast cancer and EMT cell lines. We show that transla- tionally relevant methods for increasing miR-203 abundance within a target tissue affects cellular Citation: Song, S.; Johnson, K.S.; properties associated with cancer progression. While stable miR-203 expression suppresses LASP1 Lujan, H.; Pradhan, S.H.; Sayes, C.M.; and survivin, nanoliposomal delivery suppresses BMI1, indicating that suppression of distinct mRNA Taube, J.H. Nanoliposomal Delivery target profiles can lead to loss of cancer cell migration.
    [Show full text]
  • Immune Function of Mir-214 and Its Application Prospects As Molecular Marker
    Immune function of miR-214 and its application prospects as molecular marker Qiuyuan Wang, Yang Liu, Yiru Wu, Jie Wen and Chaolai Man College of Life Science and Technology, Harbin Normal University, Harbin, China ABSTRACT MicroRNAs are a class of evolutionary conserved non-coding small RNAs that play key regulatory roles at the post-transcriptional level. In recent years, studies have shown that miR-214 plays an important role in regulating several biological processes such as cell proliferation and differentiation, tumorigenesis, inflammation and immunity, and it has become a hotspot in the miRNA field. In this review, the regulatory functions of miR-214 in the proliferation, differentiation and functional activities of immune- related cells, such as dendritic cells, T cells and NK cells, were briefly reviewed. Also, the mechanisms of miR-214 involved in tumor immunity, inflammatory regulation and antivirus were discussed. Finally, the value and application prospects of miR-214 as a molecular marker in inflammation and tumor related diseases were analyzed briefly. We hope it can provide reference for further study on the mechanism and application of miR-214. Subjects Biochemistry, Molecular Biology, Immunology Keywords miR-214, Immune cell, Tumor immunity, Inflammation, Virus, Molecular marker INTRODUCTION MicroRNAs (miRNAs) are a kind of high conserved non-coding small RNAs in evolution that bind to the 30-untranslated region (30-UTR) of target gene mRNA and regulate gene Submitted 18 September 2020 expression at post-transcriptional level. In immune responses, miRNAs act as signal- Accepted 20 January 2021 Published 16 February 2021 regulating molecules after immune-related receptors activation, and affect the expression Corresponding author of immune-related genes, thus extensively participating in various aspects of immune Chaolai Man, [email protected] response (Bosisio et al., 2019; Mehta & Baltimore, 2016).
    [Show full text]
  • ANT2 Shrna Downregulates Mir-19A and Mir-96 Through the PI3K/Akt Pathway and Suppresses Tumor Growth in Hepatocellular Carcinoma Cells
    OPEN Experimental & Molecular Medicine (2016) 48, e222; doi:10.1038/emm.2015.126 & 2016 KSBMB. All rights reserved 2092-6413/16 www.nature.com/emm ORIGINAL ARTICLE ANT2 shRNA downregulates miR-19a and miR-96 through the PI3K/Akt pathway and suppresses tumor growth in hepatocellular carcinoma cells Seung Hyun Baik1,3, Jongkuen Lee1,3, Yeong-Shin Lee1,3, Ji-Young Jang1 and Chul-Woo Kim1,2 MicroRNAs (miRNAs) are negative regulators of gene expression, and miRNA deregulation is found in various tumors. We previously reported that suppression of adenine nucleotide translocase 2 (ANT2) by short hairpin RNA (shRNA) inhibits hepatocellular carcinoma (HCC) development by rescuing miR-636 expression. However, the tumor-suppressive mechanisms of ANT2 shRNA are still poorly understood in HCC. Here, we hypothesized that miRNAs that are specifically downregulated by ANT2 shRNA might function as oncomiRs, and we investigated the roles of ANT2 shRNA-regulated miRNAs in the pathogenesis of HCC. Our data show that miR-19a and miR-96, whose expression is regulated by ANT2 suppression, were markedly upregulated in HCC cell lines and clinical samples. Ectopic expression of miR-19a and miR-96 dramatically induced the proliferation and colony formation of hepatoma cells in vitro, whereas inhibition of miR-19a and miR-96 reduced these effects. To investigate the in vivo function, we implanted miR-96-overexpressing HepG2 cells in a xenograft model and demonstrated that the increase in miR-96 promoted tumor growth. We also found that miR-19a and miR-96 inhibited expression of tissue inhibitor of metalloproteinase-2. Taken together, our results suggest that ANT2-regulated miR-19a and miR-96 play an important role in promoting the proliferation of human HCC cells, and the knockdown of ANT2 directly downregulates miR-19a and miR-96, ultimately resulting in the suppression of tumor growth.
    [Show full text]
  • Elevated Circulating Microrna-122 Is Associated with Obesity and Insulin Resistance in Young Adults
    R Wang, J Hong, Y Cao and miR-122, obesity and insulin 172:3 291–300 Clinical Study others resistance Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults Rui Wang1,*, Jie Hong1,*, Yanan Cao1,*, Juan Shi1, Weiqiong Gu1, Guang Ning1,2, Yifei Zhang1 and Weiqing Wang1 1Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors and E-Institutes of Shanghai Universities, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and 2Laboratory for Endocrine and Metabolism, Institute of Health Sciences, Correspondence Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School should be addressed of Medicine, Shanghai 200025, China to W Wang *(R Wang, J Hong and Y Cao contributed equally to this work) Email [email protected] Abstract Objective: MicroRNAs (miRNAs) are involved in the regulation of adiposity, but functional studies have yielded inconclusive results. Examining the associations of circulating miRNAs levels with obesity and insulin sensitivity in humans may lead to improved insights. Design and methods: Serum samples collected from 112 obese and control subjects (50.0% men) were randomly divided and combined into four pools (28 samples in each obese or control pool). The genome-wide circulating miRNA profiles were detected via microarray. Elevated miR-122 was selected and validated in individual serum samples from 123 obese (46.7% men) and 107 control (50.0% men) young adults. Associations between circulating miR-122 levels and parameters related to adiposity, insulin resistance, lipid profiles and hepatic enzymes were further assessed.
    [Show full text]
  • Microrna Pharmacoepigenetics: Posttranscriptional Regulation Mechanisms Behind Variable Drug Disposition and Strategy to Develop More Effective Therapy
    1521-009X/44/3/308–319$25.00 http://dx.doi.org/10.1124/dmd.115.067470 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 44:308–319, March 2016 Copyright ª 2016 by The American Society for Pharmacology and Experimental Therapeutics Minireview MicroRNA Pharmacoepigenetics: Posttranscriptional Regulation Mechanisms behind Variable Drug Disposition and Strategy to Develop More Effective Therapy Ai-Ming Yu, Ye Tian, Mei-Juan Tu, Pui Yan Ho, and Joseph L. Jilek Department of Biochemistry & Molecular Medicine, University of California Davis School of Medicine, Sacramento, California Received September 30, 2015; accepted November 12, 2015 Downloaded from ABSTRACT Knowledge of drug absorption, distribution, metabolism, and excre- we review the advances in miRNA pharmacoepigenetics including tion (ADME) or pharmacokinetics properties is essential for drug the mechanistic actions of miRNAs in the modulation of Phase I and development and safe use of medicine. Varied or altered ADME may II drug-metabolizing enzymes, efflux and uptake transporters, and lead to a loss of efficacy or adverse drug effects. Understanding the xenobiotic receptors or transcription factors after briefly introducing causes of variations in drug disposition and response has proven the characteristics of miRNA-mediated posttranscriptional gene dmd.aspetjournals.org critical for the practice of personalized or precision medicine. The regulation. Consequently, miRNAs may have significant influence rise of noncoding microRNA (miRNA) pharmacoepigenetics and on drug disposition and response. Therefore, research on miRNA pharmacoepigenomics has come with accumulating evidence sup- pharmacoepigenetics shall not only improve mechanistic under- porting the role of miRNAs in the modulation of ADME gene standing of variations in pharmacotherapy but also provide novel expression and then drug disposition and response.
    [Show full text]
  • Microrna-155 Modulates Bile Duct Inflammation by Targeting the Suppressor of Cytokine Signaling 1 in Biliary Atresia
    nature publishing group Basic Science Investigation | Articles MicroRNA-155 modulates bile duct inflammation by targeting the suppressor of cytokine signaling 1 in biliary atresia Rui Zhao1, Rui Dong1, Yifan Yang1, Yuqing Wang1, Jin Ma2, Jiang Wang1, Hao Li1 and Shan Zheng1 BACKGROUND: Biliary atresia (BA) is an etiologically etiology and pathogenesis of BA remains largely unknown. A perplexing disease, manifested by neonatal cholestasis, leading hypothesis for the pathogenesis of BA is a virus repeated cholangitis, and progressive biliary fibrosis. MiR-155 infection-initiated bile duct injury (possibly prenatal), which has been implicated to modulate the immune response, is then followed by an exaggerated inflammatory or which contributes to biliary injury. However, its potential role autoimmune response targeting the bile duct epithelium. in the pathogenesis of BA has not been addressed so far. This ultimately results in progressive bile duct injury, METHODS: The microRNA changes from BA patients and obliteration, and secondary biliary cirrhosis (3,4). controls were identified via microarray. The immunomodula- Gene expression is primarily regulated at a post- tory function of miR-155 was investigated via cell transfection transcriptional level by microRNAs (miRNAs), which exert and reporter assay. The lentiviral vector pL-miR-155 inhibitor their function by targeting complementary mRNA molecules, was transfected into a mouse model to investigate its thus inhibiting their translation by binding to the 3′ role in BA. untranslated region (UTR) (5). Many miRNAs have been RESULTS: The expression of miR-155 in livers of BA patients reported to be differentially expressed in autoimmune diseases was significantly increased, and an inverse correlation and consequently may have a pivotal role in the regulation of between miR-155 and suppressor of cytokine signaling 1 both immune responses and autoimmunity.
    [Show full text]
  • METTL1 Promotes Let-7 Microrna Processing Via M7g Methylation
    Article METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation Graphical Abstract Authors Luca Pandolfini, Isaia Barbieri, Andrew J. Bannister, ..., Mara d’Onofrio, Shankar Balasubramanian, Tony Kouzarides Correspondence [email protected] In Brief Pandolfini, Barbieri, et al. show that a subgroup of tumor suppressor microRNAs, including let-7e, contain 7-methylguanosine (m7G). Methyltransferase METTL1 is required for m7G modification of miRNAs, their efficient processing, and the inhibition of lung cancer cell migration. Structurally, m7G in miRNA precursors antagonizes RNA secondary structures that would otherwise inhibit their maturation. Highlights Data Resource d Internal m7G is identified in miRNAs by two independent GSE112182 sequencing techniques GSE112180 GSE112181 d Methyltransferase METTL1 mediates m7G modification of GSE120454 specific miRNAs GSE120455 d METTL1 promotes miRNA maturation and suppresses lung cancer cell migration d m7G promotes processing by antagonizing G-quadruplex structures in miRNA precursors Pandolfini et al., 2019, Molecular Cell 74, 1278–1290 June 20, 2019 ª 2019 The Author(s). Published by Elsevier Inc. https://doi.org/10.1016/j.molcel.2019.03.040 Molecular Cell Article METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation Luca Pandolfini,1,9 Isaia Barbieri,1,2,9 Andrew J. Bannister,1 Alan Hendrick,3 Byron Andrews,3 Natalie Webster,3 Pierre Murat,4,7 Pia Mach,1 Rossella Brandi,5 Samuel C. Robson,1,8 Valentina Migliori,1 Andrej Alendar,1 Mara d’Onofrio,5,6 Shankar Balasubramanian,4
    [Show full text]
  • Molecular Pathogenesis and Regulation of the Mir-29-3P-Family: Involvement of ITGA6 and ITGB1 in Intra-Hepatic Cholangiocarcinoma
    cancers Article Molecular Pathogenesis and Regulation of the miR-29-3p-Family: Involvement of ITGA6 and ITGB1 in Intra-Hepatic Cholangiocarcinoma Yuto Hozaka 1 , Naohiko Seki 2,* , Takako Tanaka 1, Shunichi Asai 2, Shogo Moriya 3, Tetsuya Idichi 1, Masumi Wada 1, Kiyonori Tanoue 1, Yota Kawasaki 1, Yuko Mataki 1 , Hiroshi Kurahara 1 and Takao Ohtsuka 1 1 Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; [email protected] (Y.H.); [email protected] (T.T.); [email protected] (T.I.); [email protected] (M.W.); [email protected] (K.T.); [email protected] (Y.K.); [email protected] (Y.M.); [email protected] (H.K.); [email protected] (T.O.) 2 Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; [email protected] 3 Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-43-226-2971 Simple Summary: Even today, there are no effective targeted therapies for intrahepatic cholan- giocarcinoma (ICC) patients. Clarifying the molecular pathogenesis of ICC will contribute to the Citation: Hozaka, Y.; Seki, N.; development of treatment strategies for this disease. In this study, we searched for the role of the Tanaka, T.; Asai, S.; Moriya, S.; Idichi, miR-29-3p-family and its association with oncogenic pathway. Interestingly, aberrant expression of T.; Wada, M.; Tanoue, K.; Kawasaki, ITGA6 and ITGB1 was directly regulated by the miR-29-3p-family which are involved in multiple Y.; Mataki, Y.; et al.
    [Show full text]
  • An Integrated Hypothesis for Mir-126 in Vascular Disease Authors Bo Yu1, Yinghua Jiang2, Xiaoying Wang2, Shusheng Wang1,3*
    Shusheng Wang et al. Medical Research Archives vol 8 issue 5. Medical Research Archives REVIEW ARTICLE An integrated hypothesis for miR-126 in vascular disease Authors Bo Yu1, Yinghua Jiang2, Xiaoying Wang2, Shusheng Wang1,3* Affiliations 1Department of Cell and Molecular Biology, Tulane University, 2000 Percival Stern Hall, 6400 Freret Street, New Orleans, LA, 70118, USA 2Department of Neurosurgery 3Department of Ophthalmology, Tulane University School of Medicine, 1430 Tulane Avenue, SL-69, New Orleans, LA 70112, USA Correspondence Shusheng Wang Email: [email protected] Abstract microRNA miR-126 was among the early discovered miRNAs that are expressed specifically in the vasculature and have critical functions in vascular development. Recent studies have started to unveil potentially important function of miR-126 in vascular diseases, including atherosclerosis, coronary artery disease, stroke and diabetic vasculopathy. The action of miR-126 reflects its function in angiogenesis and inflammation. The expression of miR-126 is downregulated in a variety of vascular diseases, and miR-126 overexpression appears to beneficial for most vascular disease models. In the minireview, we summarize the historic and current research regarding miR-126 function and mechanisms in the vascular system, its link to long noncoding RNAs (lncRNA), as well as the potential of miR-126-based therapeutics for vascular diseases. To explain the seemingly conflicting function of miR-126 from different studies, an integrated hypothesis is proposed that miR-126 has strand- and cell type-specific functions in angiogenesis and inflammation, making it beneficial in many different vascular disease models. Copyright 2020 KEI Journals. All Rights Reserved Shusheng Wang et al.
    [Show full text]
  • Identification and Characterization of Mir-96, a Potential Biomarker of NSCLC, Through Bioinformatic Analysis
    ONCOLOGY REPORTS 38: 1213-1223, 2017 Identification and characterization of miR-96, a potential biomarker of NSCLC, through bioinformatic analysis TONGHUI CAI*, JIE LONG*, HONGyAN WANG, WANXIA LIU and YajIE ZHANG Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China Received November 8, 2016; Accepted june 6, 2017 DOI: 10.3892/or.2017.5754 Abstract. Lung cancer is the leading cause of cancer-related Introduction death worldwide. The poor prognosis is partly due to lack of efficient methods for early diagnosis. MicroRNAs play roles Based on GIOBALCAN, an estimated 1.8 million new lung in almost all aspects of cancer biology, and can be secreted cancer cases and 1.6 million deaths occurred in 2012. This into the circulation and serve as molecular biomarkers for the makes lung cancer the leading cause of cancer-related death early diagnosis of cancer. In the present study, we determined among males worldwide and females in developed coun- the expression of miR-96 and the function of its target genes in tries (1). The poor prognosis is attributed to the lack of efficient lung cancer through bioinformatic analysis. Four microRNA methods for early diagnosis and lack of successful treatment expression profiles of lung cancer were downloaded from for metastasis. Since non-small cell lung cancer (NSCLC), Gene Expression Omnibus and the data were analyzed using which accounts for approximately 85% of all lung cancer SPSS 16.0 software. Compared to the control group, expres- cases, is not very sensitive to chemotherapy and/or radiation, sion of miR-96 was significantly increased in non-small cell surgery remains the treatment of choice.
    [Show full text]
  • Epigenetic Inactivation of Mir-203 As a Key Step in Neural Crest Epithelial-To-Mesenchymal Transition Estefanıasá ́Nchez-Vásquez1, Marianne E
    © 2019. Published by The Company of Biologists Ltd | Development (2019) 146, dev171017. doi:10.1242/dev.171017 RESEARCH ARTICLE Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition EstefanıaSá ́nchez-Vásquez1, Marianne E. Bronner2 and Pablo H. Strobl-Mazzulla1,* ABSTRACT neural crest delamination from the neural tube. These results miR-203 is a tumor-suppressor microRNA with known functions in demonstrate an additional level of fine tuning and an important role cancer metastasis. Here, we explore its normal developmental role in for epigenetic regulators during neural crest EMT, raising the the context of neural crest development. During the epithelial-to- intriguing possibility that other yet to be identified factors may be mesenchymal transition of neural crest cells to emigrate from the involved. neural tube, miR-203 displays a reciprocal expression pattern with In recent years, microRNAs (miRNAs) have been shown to be key regulators of neural crest delamination, Phf12 and Snail2, and key regulators of EMT in several tumor cells (Diaz-Lopez et al., ∼ interacts with their 3′UTRs. We show that ectopic maintenance of 2014; Ding, 2014; Xia and Hui, 2012). MicroRNAs are 22- miR-203 inhibits neural crest migration in chick, whereas its functional nucleotide single-stranded RNAs that negatively regulate gene inhibition using a ‘sponge’ vector or morpholinos promotes premature expression post-transcriptionally (Kloosterman and Plasterk, 2006) neural crest delamination. Bisulfite sequencing further shows that by inhibiting translation and/or causing degradation by binding to ′ ′ epigenetic repression of miR-203 is mediated by the de novo DNA complementary sequences located at the 3 -untranslated region (3 - methyltransferase DNMT3B, the recruitment of which to regulatory UTR) of target mRNAs.
    [Show full text]
  • Mono-Uridylation of Pre-Microrna As a Key Step in the Biogenesis of Group II Let-7 Micrornas
    Mono-Uridylation of Pre-MicroRNA as a Key Step in the Biogenesis of Group II let-7 MicroRNAs Inha Heo,1,2,3 Minju Ha,1,2,3 Jaechul Lim,1,2 Mi-Jeong Yoon,2 Jong-Eun Park,1,2 S. Chul Kwon,1,2 Hyeshik Chang,1,2 and V. Narry Kim1,2,* 1Institute for Basic Science 2School of Biological Sciences Seoul National University, Seoul 151-742, Korea 3These authors contributed equally to this work *Correspondence: [email protected] http://dx.doi.org/10.1016/j.cell.2012.09.022 SUMMARY hairpin (Denli et al., 2004; Gregory et al., 2004; Han et al., 2004, 2006; Landthaler et al., 2004). Like other RNase-III-type RNase III Drosha initiates microRNA (miRNA) matu- endonucleases, Drosha introduces a staggered cut such that ration by cleaving a primary miRNA transcript and the product acquires a characteristic 2 nt overhang at the 30 releasing a pre-miRNA with a 2 nt 30 overhang. Dicer terminus. After cleavage, the pre-miRNA is exported to the recognizes the 2 nt 30 overhang structure to selec- cytoplasm by exportin 5 in a complex with Ran-GTP (Bohnsack tively process pre-miRNAs. Here, we find that, unlike et al., 2004; Lund et al., 2004; Yi et al., 2003). The cytoplasmic prototypic pre-miRNAs (group I), group II pre- RNase III Dicer processes the pre-miRNA further to liberate a small RNA duplex (Bernstein et al., 2001; Grishok et al., miRNAs acquire a shorter (1 nt) 30 overhang from 0 2001; Hutva´ gner et al., 2001; Ketting et al., 2001; Knight and Drosha processing and therefore require a 3 -end Bass, 2001).
    [Show full text]