PMID- 37543219
OWN - NLM
STAT- MEDLINE
DCOM- 20230913
LR  - 20230913
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 884
DP  - 2023 Oct 30
TI  - CircCDK1 blocking IGF2BP2-mediated m6A modification of CPPED1 promotes laryngeal 
      squamous cell carcinoma metastasis via the PI3K/AKT signal pathway.
PG  - 147686
LID - S0378-1119(23)00527-9 [pii]
LID - 10.1016/j.gene.2023.147686 [doi]
AB  - BACKGROUND: Circular RNA (circRNA) is a novel noncoding RNA (ncRNA) that plays a 
      critical role in various cancers. However, the clinical significance, biological 
      function, and molecular mechanisms of circRNAs in laryngeal squamous cell 
      carcinoma (LSCC) remain unclear. METHODS: A circRNA array was performed to 
      identify the differentially expressed circRNAs. In vitro and in vivo assays were 
      proceeded to verify the biological function of circCDK1 in LSCC. RNA pulldown 
      assays and RNA immunoprecipitation (RIP) were used to confirm the binding between 
      circCDK1 and insulin-like growth factor 2 mRNA binding protein 2(IGF2BP2). The 
      MeRIP assay was then used to identified the N6-methyladenisine (m6A) methylation 
      of calcineurin like phosphatase domain containing1 (CPPED1). RESULTS: 
      Hsa_circ_0005774 (circCDK1) was found upregulated in LSCC tissues compared to 
      adjacent normal tissues. The level of circCDK1 was positively correlated with 
      poor prognosisof LSCC patients. In vitro and in vivo, circCDK1 promoted migration 
      and invasion of LSCC cells. Mechanistically, eukaryotic translation initiation 
      factor4A3(EIF4A3) induced biogenesis of circCDK1 by binding to its flanking. By 
      competitively binding to IGF2BP2, circCDK1 blocked the m6A modification of CPPED1 
      in IGF2BP2-dependent manner. Moreover, the circCDK1-mediated decrease of CPPED1 
      activated the PI3K/AKT signal pathway to facilitate progression of LSCC. 
      CONCLUSIONS: Our findings demonstrated that EIF4A3-induced upregulation of 
      circCDK1 promoted LSCC metastasis via EIF4A3-circCDK1-IGF2BP2-CPPED1 to activate 
      PI3K-AKT signal pathway. CircCDK1 might serve as a new diagnostic and prognostic 
      marker or potential therapeutic target for LSCC.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Li, Jinling
AU  - Li J
AD  - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical 
      University, Shijiazhuang, Hebei, China.
FAU - Cao, Huan
AU  - Cao H
AD  - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical 
      University, Shijiazhuang, Hebei, China.
FAU - Yang, Jianwang
AU  - Yang J
AD  - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical 
      University, Shijiazhuang, Hebei, China.
FAU - Wang, Baoshan
AU  - Wang B
AD  - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical 
      University, Shijiazhuang, Hebei, China. Electronic address: hebwangbs@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230803
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.6.1.- (EIF4A3 protein, human)
RN  - EC 2.7.7.- (Eukaryotic Initiation Factor-4A)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
RN  - 0 (IGF2BP2 protein, human)
SB  - IM
MH  - Humans
MH  - Squamous Cell Carcinoma of Head and Neck/genetics
MH  - *MicroRNAs/genetics
MH  - RNA, Circular/genetics
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - *Laryngeal Neoplasms/genetics/pathology
MH  - *Carcinoma, Squamous Cell/genetics/pathology
MH  - Cell Line, Tumor
MH  - Signal Transduction/genetics
MH  - *Head and Neck Neoplasms/genetics
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Eukaryotic Initiation Factor-4A/genetics/metabolism
MH  - DEAD-box RNA Helicases/genetics
OTO - NOTNLM
OT  - CPPED1
OT  - CircCDK1
OT  - IGF2BP2
OT  - Laryngeal squamous cell carcinoma
OT  - Metastasis
OT  - N6-methyladenisine methylation
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/08/06 05:42
MHDA- 2023/09/13 06:42
CRDT- 2023/08/05 19:15
PHST- 2023/05/12 00:00 [received]
PHST- 2023/07/05 00:00 [revised]
PHST- 2023/08/01 00:00 [accepted]
PHST- 2023/09/13 06:42 [medline]
PHST- 2023/08/06 05:42 [pubmed]
PHST- 2023/08/05 19:15 [entrez]
AID - S0378-1119(23)00527-9 [pii]
AID - 10.1016/j.gene.2023.147686 [doi]
PST - ppublish
SO  - Gene. 2023 Oct 30;884:147686. doi: 10.1016/j.gene.2023.147686. Epub 2023 Aug 3.