PMID- 36355210
OWN - NLM
STAT- MEDLINE
DCOM- 20230202
LR  - 20230202
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Linking)
VI  - 149
IP  - 1
DP  - 2023 Jan
TI  - miRNA-223-3p regulates ECT2 to promote proliferation, invasion, and metastasis of 
      gastric cancer through the Wnt/beta-catenin signaling pathway.
PG  - 121-134
LID - 10.1007/s00432-022-04453-9 [doi]
AB  - PURPOSE: Expression of the guanine nucleotide exchange factor epithelial cell 
      transforming 2 (ECT2) is elevated in gastric cancer (GC) but its biological 
      function in GC is poorly understood. MicroRNAs (miRNAs) have great potential as 
      therapeutic targets for GC through their ability to modulate gene expression. In 
      the present study, we sought to identify potential miRNA-mRNA-protein regulatory 
      pathways that might control ECT2 expression and function in GC. METHODS: ECT2 
      expression was examined in clinical GC specimens by immunohistochemical staining, 
      and protein levels were correlated with clinicopathological features and 
      prognosis. TargetScan was used to identify potential ECT2 mRNA-complementary 
      miRNAs, and the roles of ECT2 and miRNA-223-3p (miR-223-3p) in GC cell biology 
      and signaling pathway activation were examined by targeted knockdown (KD) or 
      overexpression (OE) of ECT2 and miR-223-3p in GC cell lines. A murine GC 
      xenograft model was developed to explore the impact of ECT2 OE on tumor growth in 
      vivo. RESULTS: ECT2 expression was significantly elevated in GC specimens 
      compared with normal gastric tissues and the level correlated positively with 
      depth of invasion, ulceration, vascular tumor thrombus, neural invasion, and 
      lymph node metastasis (p < 0.05). ECT2 was an independent prognostic factor for 
      overall survival of GC patients (high ECT2 expression v.s. low ECT2 expression: 
      chi(2) = 29.831, p < 0.001). ECT2 KD or miR-223-3p OE markedly suppressed the 
      proliferation, migration, and invasion of GC cells in vitro, whereas ECT2 OE had 
      the opposite effects. ECT2 OE also promoted the growth of GC tumors in vivo. 
      Tumor expression of Wnt2, beta-catenin, and several downstream target proteins in GC 
      cells were decreased by ECT2 KD or miR-223-3p OE but increased by ECT2 OE. 
      CONCLUSIONS: miR-223-3p regulates ECT2 expression to promote tumorigenic behavior 
      of GC via activation of the Wnt/beta-catenin signaling pathway, suggesting that ECT2 
      and miR-223-3p as potential therapeutic targets for GC.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Li, Lin
AU  - Li L
AD  - Departments of Gastroenterology, The First Affiliated Hospital of Soochow 
      University, Suzhou, 215006, Jiangsu, People's Republic of China.
AD  - Departments of Gastroenterology, The First Affiliated Hospital of Wannan Medical 
      College, Wuhu, 241001, Anhui, People's Republic of China.
FAU - Liu, Pengwei
AU  - Liu P
AD  - Departments of Gastroenterology, The First Affiliated Hospital of Wannan Medical 
      College, Wuhu, 241001, Anhui, People's Republic of China.
FAU - He, Chiyi
AU  - He C
AD  - Departments of Gastroenterology, The First Affiliated Hospital of Wannan Medical 
      College, Wuhu, 241001, Anhui, People's Republic of China.
FAU - Xu, Chunfang
AU  - Xu C
AD  - Departments of Gastroenterology, The First Affiliated Hospital of Soochow 
      University, Suzhou, 215006, Jiangsu, People's Republic of China. xcf601@163.com.
LA  - eng
GR  - No.2021cg36/Wuhu City Science and Technology Project/
GR  - No.2021yf63/Wuhu City Science and Technology Project/
GR  - No.2021cg45/Wuhu City Science and Technology Project/
GR  - No.WK2022ZF03/Key Research Project of Wannan Medical College/
GR  - No.WK2021ZF18/Key Research Project of Wannan Medical College/
PT  - Journal Article
DEP - 20221110
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (MicroRNAs)
RN  - 0 (Proteins)
RN  - 0 (ECT2 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (MIRN223 microRNA, human)
RN  - 0 (MIRN223 microRNA, mouse)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Stomach Neoplasms/pathology
MH  - Wnt Signaling Pathway/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Cell Line, Tumor
MH  - *MicroRNAs/genetics/metabolism
MH  - Proteins/genetics
MH  - Epithelial Cells/pathology
MH  - Cell Proliferation/genetics
MH  - Cell Movement/genetics
MH  - Proto-Oncogene Proteins/genetics/metabolism
OTO - NOTNLM
OT  - ECT2
OT  - Gastric cancer
OT  - Wnt/beta-catenin signaling pathway
OT  - miR-223-3p
EDAT- 2022/11/11 06:00
MHDA- 2023/02/03 06:00
CRDT- 2022/11/10 11:16
PHST- 2022/08/10 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/11/11 06:00 [pubmed]
PHST- 2023/02/03 06:00 [medline]
PHST- 2022/11/10 11:16 [entrez]
AID - 10.1007/s00432-022-04453-9 [pii]
AID - 10.1007/s00432-022-04453-9 [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2023 Jan;149(1):121-134. doi: 
      10.1007/s00432-022-04453-9. Epub 2022 Nov 10.