PMID- 32923135
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20230919
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 9
IP  - 1
DP  - 2020 Jun 3
TI  - Identification of miR-200a-5p targeting the peptide transporter TAP1 and its 
      association with the clinical outcome of melanoma patients.
PG  - 1774323
LID - 10.1080/2162402X.2020.1774323 [doi]
LID - 1774323
AB  - Tumor escape is often associated with abnormalities in the surface expression of 
      the human leukocyte antigen class I (HLA-I) antigens thereby limiting CD8(+) 
      cytotoxic T cell responses. This impaired HLA-I surface expression can be 
      mediated by deficient expression of components of the antigen processing and 
      presentation machinery (APM) due to epigenetic, transcriptional and/or 
      post-transcriptional processes. Since a discordant mRNA and protein expression 
      pattern of APM components including the peptide transporter associated with 
      antigen processing 1 (TAP1) has been frequently described in tumors of distinct 
      origin, a post-transcriptional control of APM components caused by microRNAs 
      (miR) was suggested. Using an in silico approach, miR-200a-5p has been identified 
      as a candidate miR binding to the 3' untranslated region (UTR) of TAP1. 
      Luciferase reporter assays demonstrated a specific binding of miR-200a-5p to the 
      TAP1 3'-UTR. Furthermore, the miR-200a-5p expression is inversely correlated with 
      the TAP1 protein expression in HEK293T cells and in a panel of melanoma cell 
      lines as well as in primary melanoma lesions. High levels of miR-200a-5p 
      expression were associated with a shorter overall survival of melanoma patients. 
      Overexpression of miR-200a-5p reduced TAP1 levels, which was accompanied by a 
      decreased HLA-I surface expression and an enhanced NK cell sensitivity of 
      melanoma cells. These data show for the first time a miR-mediated control of the 
      peptide transporter subunit TAP1 in melanoma thereby leading to a reduced HLA-I 
      surface expression accompanied by an altered immune recognition and reduced 
      patients' survival. ABBREVIATIONS: Ab: antibody; ACTB: beta-actin; APM: antigen 
      processing and presentation machinery; ATCC: American tissue culture collection; 
      beta(2)-m: beta(2)-microglobulin; BSA: bovine serum albumin; CTL: cytotoxic T 
      lymphocyte; FCS: fetal calf serum; FFL: firefly luciferase; FFPE: formalin-fixed 
      paraffin-embedded; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HC: heavy 
      chain; HLA: human leukocyte antigen; HLA-I: HLA class I; HRP: horseradish 
      peroxidase; IFN: interferon; im-miR: immune modulatory miRNA; LMP: low molecular 
      weight protein; luc: luciferase; MFI: mean fluorescence intensity; MHC: major 
      histocompatibility complex; miR: microRNA; NC: negative control; NK: natural 
      killer; NSCLC: non-small cell lung carcinoma; OS: overall survival; PBMC: 
      peripheral blood mononuclear cells; RBP: RNA-binding proteins; RL: Renilla; RLU: 
      relative light units; TAP: transporter associated with antigen processing; tpn: 
      tapasin; UTR: untranslated region.
CI  - (c) 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
FAU - Lazaridou, Maria-Filothei
AU  - Lazaridou MF
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
FAU - Gonschorek, Evamaria
AU  - Gonschorek E
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
FAU - Massa, Chiara
AU  - Massa C
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
FAU - Friedrich, Michael
AU  - Friedrich M
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
FAU - Handke, Diana
AU  - Handke D
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
FAU - Mueller, Anja
AU  - Mueller A
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
FAU - Jasinski-Bergner, Simon
AU  - Jasinski-Bergner S
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
FAU - Dummer, Reinhard
AU  - Dummer R
AD  - Institute of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Koelblinger, Peter
AU  - Koelblinger P
AD  - Department of Dermatology and Allergology, University Hospital Salzburg, 
      Salzburg, Austria.
FAU - Seliger, Barbara
AU  - Seliger B
AUID- ORCID: 0000-0002-5544-4958
AD  - Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 
      Halle, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200603
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (MicroRNAs)
RN  - 0 (Peptide Transporter 1)
RN  - 0 (TAP1 protein, human)
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2/genetics
MH  - Antigen Presentation
MH  - HEK293 Cells
MH  - Humans
MH  - Leukocytes, Mononuclear
MH  - *Melanoma/genetics
MH  - *MicroRNAs/genetics
MH  - Peptide Transporter 1
PMC - PMC7458634
OTO - NOTNLM
OT  - HLA
OT  - Peptide transporter
OT  - immune escape
OT  - microRNA
OT  - tumor
EDAT- 2020/09/15 06:00
MHDA- 2020/09/15 06:01
PMCR- 2020/06/03
CRDT- 2020/09/14 05:53
PHST- 2020/09/14 05:53 [entrez]
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2020/09/15 06:01 [medline]
PHST- 2020/06/03 00:00 [pmc-release]
AID - 1774323 [pii]
AID - 10.1080/2162402X.2020.1774323 [doi]
PST - epublish
SO  - Oncoimmunology. 2020 Jun 3;9(1):1774323. doi: 10.1080/2162402X.2020.1774323.