PMID- 34356658
OWN - NLM
STAT- MEDLINE
DCOM- 20211006
LR  - 20211006
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 11
IP  - 7
DP  - 2021 Jul 15
TI  - Loss of the MAF Transcription Factor in Laryngeal Squamous Cell Carcinoma.
LID - 10.3390/biom11071035 [doi]
LID - 1035
AB  - MAF is a transcription factor that may act either as a tumor suppressor or as an 
      oncogene, depending on cell type. We have shown previously that the overexpressed 
      miR-1290 influences MAF protein levels in LSCC (laryngeal squamous cell 
      carcinoma) cell lines. In this study, we shed further light on the interaction 
      between miR-1290 and MAF, as well as on cellular MAF protein localization in 
      LSCC. We confirmed the direct interaction between miR-1290 and MAF 3'UTR by a 
      dual-luciferase reporter assay. In addition, we used immunohistochemistry 
      staining to analyze MAF protein distribution and observed loss of MAF nuclear 
      expression in 58% LSCC samples, of which 10% showed complete absence of MAF, 
      compared to nuclear and cytoplasmatic expression in 100% normal mucosa. Using 
      TCGA data, bisulfite pyrosequencing and CNV analysis, we excluded the possibility 
      that loss-of-function mutations, promoter region DNA methylation or CNV are 
      responsible for MAF loss in LSCC. Finally, we identified genes involved in the 
      regulation of apoptosis harboring the MAF binding motif in their promoter region 
      by applied FIMO and DAVID GO analysis. Our results highlight the role of miR-1290 
      in suppressing MAF expression in LSCC. Furthermore, MAF loss or mislocalization 
      in FFPE LSCC tumor samples might suggest that MAF acts as a LSCC tumor suppressor 
      by regulating apoptosis.
FAU - Janiszewska, Joanna
AU  - Janiszewska J
AUID- ORCID: 0000-0002-1765-0152
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
FAU - Bodnar, Magdalena
AU  - Bodnar M
AD  - Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus 
      Copernicus University in Torun, 85-094 Bydgoszcz, Poland.
FAU - Paczkowska, Julia
AU  - Paczkowska J
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
FAU - Ustaszewski, Adam
AU  - Ustaszewski A
AUID- ORCID: 0000-0002-9542-0029
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
FAU - Smialek, Maciej J
AU  - Smialek MJ
AUID- ORCID: 0000-0002-8042-7965
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
FAU - Szylberg, Lukasz
AU  - Szylberg L
AD  - Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus 
      Copernicus University in Torun, 85-094 Bydgoszcz, Poland.
AD  - Department of Oncologic Pathology, Cancer Center, 85-796 Bydgoszcz, Poland.
FAU - Marszalek, Andrzej
AU  - Marszalek A
AUID- ORCID: 0000-0002-6055-9151
AD  - Department of Oncologic Pathology and Prophylactics, Poznan University of Medical 
      Sciences and Greater Poland Cancer Center, 61-866 Poznan, Poland.
FAU - Kiwerska, Katarzyna
AU  - Kiwerska K
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
AD  - Department of Tumor Pathology, Greater Poland Cancer Centre, 61-866 Poznan, 
      Poland.
FAU - Grenman, Reidar
AU  - Grenman R
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Turku University and 
      Turku University Hospital, 20-500 Turku, Finland.
FAU - Szyfter, Krzysztof
AU  - Szyfter K
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
FAU - Wierzbicka, Malgorzata
AU  - Wierzbicka M
AUID- ORCID: 0000-0003-0006-6352
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
AD  - Department of Otolaryngology and Laryngological Oncology, Poznan University of 
      Medical Sciences, 60-355 Poznan, Poland.
FAU - Giefing, Maciej
AU  - Giefing M
AUID- ORCID: 0000-0002-4760-8246
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
FAU - Jarmuz-Szymczak, Malgorzata
AU  - Jarmuz-Szymczak M
AD  - Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
AD  - Department of Hematology and Bone Marrow Transplantation, Poznan University of 
      Medical Sciences, 61-569 Poznan, Poland.
LA  - eng
GR  - Scholarship support for Ph.D. students specializing in majors strategic for 
      Greater Poland's de-velopment for year 2013/2014, Sub-measure 8.2.2 Human Capital 
      Operational Program./European Union under the European Social Fund/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210715
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MAF protein, human)
RN  - 0 (MIRN1290 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins c-maf)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Aged
MH  - Cell Line, Tumor
MH  - Cell Nucleus/genetics/metabolism
MH  - DNA Methylation
MH  - Female
MH  - Gene Dosage
MH  - Gene Expression Regulation, Neoplastic
MH  - Head and Neck Neoplasms/*genetics/pathology
MH  - Humans
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Mutation
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins c-maf/*genetics/metabolism
MH  - Squamous Cell Carcinoma of Head and Neck/*genetics/pathology
PMC - PMC8301809
OTO - NOTNLM
OT  - MAF
OT  - apoptosis
OT  - laryngeal squamous cell carcinoma
OT  - miR-1290
OT  - microRNAs
OT  - transcription factor
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/07 06:00
MHDA- 2021/10/07 06:00
PMCR- 2021/07/15
CRDT- 2021/08/06 12:20
PHST- 2021/02/22 00:00 [received]
PHST- 2021/07/08 00:00 [revised]
PHST- 2021/07/12 00:00 [accepted]
PHST- 2021/08/06 12:20 [entrez]
PHST- 2021/08/07 06:00 [pubmed]
PHST- 2021/10/07 06:00 [medline]
PHST- 2021/07/15 00:00 [pmc-release]
AID - biom11071035 [pii]
AID - biomolecules-11-01035 [pii]
AID - 10.3390/biom11071035 [doi]
PST - epublish
SO  - Biomolecules. 2021 Jul 15;11(7):1035. doi: 10.3390/biom11071035.