PMID- 38147910
OWN - NLM
STAT- MEDLINE
DCOM- 20240308
LR  - 20240308
IS  - 1880-3865 (Electronic)
IS  - 1349-0079 (Linking)
VI  - 66
IP  - 1
DP  - 2024 Mar
TI  - Suppression of KLF5 basal expression in oral carcinoma-derived cells through 
      three intact CREB1-binding sites in the silencer region.
PG  - 217-224
LID - S1349-0079(23)00197-4 [pii]
LID - 10.1016/j.job.2023.12.006 [doi]
AB  - OBJECTIVES: Kruppel-like factor (KLF)5, which is overexpressed in carcinomas such 
      as oral cancer, inhibits epidermal differentiation. KLF5 induces 
      dedifferentiation of carcinoma cells, which effectuates carcinoma progression; 
      nevertheless, the regulatory mechanism affecting the transcription of the KLF5 
      gene remains ambiguous. METHODS: Transcriptional activity of the KLF5 silencer, 
      specifically the 425-bp region (425-region), was examined using reporter assays. 
      An additional analysis was conducted to assess the impact of the minimal 
      essential region (MER) of KLF5 on its basal expression. The affinity of cAMP 
      responsive element binding protein 1 (CREB1) for three potential CREB1-binding 
      sites in the 425-region was analyzed using DNA pull-down and quantitative 
      chromatin immunoprecipitation assays. Reporter assays employing a human oral 
      squamous carcinoma cell line, HSC2, transfected with small interfering RNA or 
      complementary DNA for CREB1, were performed to investigate the effect of CREB1 
      binding sites on MER activity. RESULTS: The 425-region exhibited no 
      transcriptional activity and suppressed MER transcriptional activity. This region 
      encodes three putative CREB1-binding sites, and CREB1 demonstrated equal binding 
      affinity for all three sites. The deletion of each of these binding sites reduced 
      CREB1 precipitation and enhanced MER activity. Endogenous CREB1 knockdown and 
      overexpression elevated and reduced MER activity, respectively, at the intact 
      sites. Conversely, site deletion hampered and improved MER activity upon CREB1 
      knockdown and overexpression, respectively. CONCLUSIONS: Suppression of KLF5 
      basal expression via CREB1 binding to the 425-region requires all three 
      CREB1-binding sites to remain intact in oral carcinoma cells. Consequently, 
      deletion of the CREB1-binding site relieves suppression of KLF5 basal expression.
CI  - Copyright (c) 2023 Japanese Association for Oral Biology. Published by Elsevier 
      B.V. All rights reserved.
FAU - Katsuumi, Reiichi
AU  - Katsuumi R
AD  - Department of Biochemistry, The Nippon Dental University School of Life Dentistry 
      at Tokyo, Japan.
FAU - Negishi, Tsubasa
AU  - Negishi T
AD  - Department of Biochemistry, The Nippon Dental University School of Life Dentistry 
      at Tokyo, Japan.
FAU - Imai, Kazushi
AU  - Imai K
AD  - Department of Biochemistry, The Nippon Dental University School of Life Dentistry 
      at Tokyo, Japan.
FAU - Mihara, Nozomi
AU  - Mihara N
AD  - Department of Biochemistry, The Nippon Dental University School of Life Dentistry 
      at Tokyo, Japan. Electronic address: leschang@tky.ndu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20231224
PL  - Netherlands
TA  - J Oral Biosci
JT  - Journal of oral biosciences
JID - 101226721
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (CREB1 protein, human)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (KLF5 protein, human)
SB  - IM
MH  - Humans
MH  - Cell Line, Tumor
MH  - Kruppel-Like Transcription Factors/genetics/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Binding Sites/genetics
MH  - *Mouth Neoplasms/genetics
MH  - *Carcinoma/genetics
MH  - Cyclic AMP Response Element-Binding Protein/genetics/metabolism
OTO - NOTNLM
OT  - CREB1
OT  - Carcinoma
OT  - Gene expression
OT  - KLF5
OT  - Transcription factors
COIS- Declaration of competing interest The authors have no conflicts of interest to 
      report.
EDAT- 2023/12/27 00:41
MHDA- 2024/03/08 06:42
CRDT- 2023/12/26 19:15
PHST- 2023/10/16 00:00 [received]
PHST- 2023/12/19 00:00 [revised]
PHST- 2023/12/20 00:00 [accepted]
PHST- 2024/03/08 06:42 [medline]
PHST- 2023/12/27 00:41 [pubmed]
PHST- 2023/12/26 19:15 [entrez]
AID - S1349-0079(23)00197-4 [pii]
AID - 10.1016/j.job.2023.12.006 [doi]
PST - ppublish
SO  - J Oral Biosci. 2024 Mar;66(1):217-224. doi: 10.1016/j.job.2023.12.006. Epub 2023 
      Dec 24.