PMID- 38321126
OWN - NLM
STAT- MEDLINE
DCOM- 20240208
LR  - 20240210
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Feb 6
TI  - IGF2BP2-m6A-circMMP9 axis recruits ETS1 to promote TRIM59 transcription in 
      laryngeal squamous cell carcinoma.
PG  - 3014
LID - 10.1038/s41598-024-53422-4 [doi]
LID - 3014
AB  - Laryngeal squamous cell carcinoma (LSCC) is a common malignancy of the head and 
      neck. Recently, circular RNA (circRNA) has been studied extensively in 
      multisystem diseases. However, there are few research on biological functions and 
      molecular mechanisms of circRNAs in LSCC. CircRNA array was used to detect the 
      differentially expressed circRNAs. Kaplan-Meier and cox regression analysis were 
      used to identify survival based on circMMP9. The qRT-PCR, RNase R treatment, 
      sanger sequencing and in situ hybridization were used to verify circMMP9 
      expression, characteristics and localization in LSCC tissues and cells. 
      Functionally, colony formation, MTS, transwell and in vivo assays were proceeded 
      to detect the biological function of circMMP9 in LSCC progression. The RNA-seq 
      was conducted to identify the molecular targets of circMMP9. Mechanically, MeRIP, 
      RNA Immunoprecipitation (RIP), RNA pulldown, Chromatin immunoprecipitation (ChIP) 
      and dual-luciferase reporter assays were carried on to verify the regulatory 
      mechanism of circMMP9. CircMMP9 was discovered upregulated in LSCC tissues and 
      cells, and high level of circMMP9 was associated with poor prognosis, low degree 
      of pathological grading, high TNM stage and lymph node metastasis of LSCC. 
      CircMMP9 knockdown prevented LSCC progression both in vitro and in vivo, whereas, 
      circMMP9 overexpression had the opposite effect. CircMMP9 was stabilized by 
      IGF2BP2 in m6A-dependent manner. TRIM59 was identified as downstream target of 
      circMMP9. CircMMP9 recruited ETS1 to stimulate TRIM59 transcription. Moreover, 
      TRIM59 accelerated LSCC progression via activating the PI3K/AKT signal pathway. 
      Our findings offered a unique regulatory mechanism for circMMP9 in LSCC, as well 
      as a novel proof that circMMP9 may be utilize as a diagnostic marker and 
      therapeutic target for LSCC patients.
CI  - (c) 2024. The Author(s).
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. hebwangbs@163.com.
LA  - eng
GR  - 81972553/Project of National Natural Science Foundation of China/
GR  - H2022206376/The Natural Science Foundation of Hebei Province/
GR  - 20577716D/Special Project of Clinical Medical Research Center of Department of 
      Science and Technology of Hebei Province/
PT  - Journal Article
DEP - 20240206
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - W7IBY2BGAX (6-methyladenine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (ETS1 protein, human)
RN  - 0 (Proto-Oncogene Protein c-ets-1)
RN  - 0 (IGF2BP2 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (TRIM59 protein, human)
RN  - 0 (Tripartite Motif Proteins)
RN  - JAC85A2161 (Adenine)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
SB  - IM
MH  - Humans
MH  - Squamous Cell Carcinoma of Head and Neck/genetics
MH  - *MicroRNAs/genetics
MH  - RNA, Circular/genetics
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Carcinoma, Squamous Cell/pathology
MH  - *Laryngeal Neoplasms/pathology
MH  - *Head and Neck Neoplasms/genetics
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Cell Line, Tumor
MH  - Proto-Oncogene Protein c-ets-1/genetics
MH  - RNA-Binding Proteins/metabolism
MH  - *Tripartite Motif Proteins
MH  - Adenine/*analogs & derivatives
MH  - *Intracellular Signaling Peptides and Proteins
PMC - PMC10847447
COIS- The authors declare no competing interests.
EDAT- 2024/02/07 00:42
MHDA- 2024/02/08 06:42
PMCR- 2024/02/06
CRDT- 2024/02/06 23:22
PHST- 2023/10/11 00:00 [received]
PHST- 2024/01/31 00:00 [accepted]
PHST- 2024/02/08 06:42 [medline]
PHST- 2024/02/07 00:42 [pubmed]
PHST- 2024/02/06 23:22 [entrez]
PHST- 2024/02/06 00:00 [pmc-release]
AID - 10.1038/s41598-024-53422-4 [pii]
AID - 53422 [pii]
AID - 10.1038/s41598-024-53422-4 [doi]
PST - epublish
SO  - Sci Rep. 2024 Feb 6;14(1):3014. doi: 10.1038/s41598-024-53422-4.