PMID- 34274912
OWN - NLM
STAT- MEDLINE
DCOM- 20211021
LR  - 20220311
IS  - 2146-3131 (Electronic)
IS  - 2146-3123 (Print)
IS  - 2146-3123 (Linking)
VI  - 38
IP  - 4
DP  - 2021 Jul
TI  - CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer 
      Through Regulating VEGFA/VEGFR2 Signaling.
PG  - 229-238
LID - 10.5152/balkanmedj.2021.21145 [doi]
AB  - BACKGROUND: Circular RNAs (CircRNAs) have been recently implicated in the 
      progression of pancreatic cancer (PC). AIMS: To investigate the involvement of 
      CircCCT3 in PC and studying its interactions and functioning during the 
      progression of PC in vitro and in vivo, using methods of molecular biology and 
      bioinformatics. STUDY DESIGN: Experimental study. METHODS: The expressions of 
      CircCCT3 and miR-613 in pancreatic carcinoma tissues and cell lines were 
      evaluated by quantitative real-time polymerase chain reaction (PCR). The 
      relationship between clinical pathologic features as well as the survival rate 
      and CircCCT3 expression was analyzed with chi-square test and the Kaplan-Meier 
      method. CCK-8, wound healing, transwell assays, and the fluorescein 
      isothiocyanate- AnnexinV/propidium iodide (FITC-AnnexinV/PI) assay were used to 
      assess cell proliferation, migration, invasion, and apoptosis after CircCCT3 
      overexpression or downregulation. The Dual- Luciferase reporter assay, RNA 
      immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization 
      (FISH) assays were performed to validate the potential interaction of CircCCT3, 
      miR-613, and vascular endothelial growth factor (VEGFA). The nude mouse xenograft 
      tumor assay was used to detect CircCCT3 effects on pancreatic tumorigenesis in 
      vivo. Western blotting analysis was performed to examine the VEGFA and the 
      vascular endothelial growth factor receptor 2 (VEGFR2) protein expressions 
      following. RESULTS: CircCCT3 expression was significantly increased in PC tissues 
      (3.41 +/- 0.57 vs. 1.00 +/- 0.10, P < .01) and cell lines (Patu8988 2.57 +/- 0.20; 
      SW1990 2.88 +/- 0.10; BxPC-3 2.45 +/- 0.20; Panc02 2.99 +/- 0.10 vs. H6c7 1.00 +/- 0.10; 
      all P < .001). CircCCT3 expression was negatively correlated with miR-613 
      expression. PC patients with high CircCCT3 expression exhibited significantly 
      poorer overall survival rate than those patients with low CircCCT3 expression (P 
      = .013). Moreover, it was found that CircCCT3 promoted cell proliferation, 
      migration, and invasion, and inhibited cell apoptosis in PC cells. The CircCCT3 
      acted as a sponge for the miR-613 to facilitate VEGFA and VEGFR2 expression. 
      si-CirCCT3 also inhibited tumor growth of PC in nude mice. si-CircCCT3 reduced 
      VEGFA and VEGFR2 expression, whereas overexpression of CircCCT3 increased VEGFA 
      and VEGFR2 expression. CONCLUSION: Increased CircCCT3 suggests a poor prognosis 
      for PC patients and promotes the migration and invasion through targeting 
      VEGFA/VEGFR2 signaling. CircCCT3 may serve as a potential and promising 
      therapeutic target for PC treatment.
FAU - Hou, Ji-Ping
AU  - Hou JP
AD  - Department of General Surgery, Tianjin Baodi Hospital, Baodi Clinical College of 
      Tianjin Medical University, China.
FAU - Men, Xue-Bo
AU  - Men XB
AD  - Department of General Surgery, Tianjin Baodi Hospital, Baodi Clinical College of 
      Tianjin Medical University, China.
FAU - Yang, Lian-Ying
AU  - Yang LY
AD  - Department of General Surgery, Tianjin Baodi Hospital, Baodi Clinical College of 
      Tianjin Medical University, China.
FAU - Han, En-Kun
AU  - Han EK
AD  - Department of General Surgery, Tianjin Baodi Hospital, Baodi Clinical College of 
      Tianjin Medical University, China.
FAU - Han, Chun-Qi
AU  - Han CQ
AD  - Department of General Surgery, Tianjin Baodi Hospital, Baodi Clinical College of 
      Tianjin Medical University, China.
FAU - Liu, Li-Bin
AU  - Liu LB
AD  - Department of General Surgery, Tianjin Baodi Hospital, Baodi Clinical College of 
      Tianjin Medical University, China.
LA  - eng
PT  - Journal Article
PL  - Turkey
TA  - Balkan Med J
JT  - Balkan medical journal
JID - 101571817
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MIRN613 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.1 (KDR protein, human)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Biomarkers, Tumor/analysis
MH  - Cell Line
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Male
MH  - MicroRNAs/*antagonists & inhibitors
MH  - Middle Aged
MH  - Pancreatic Neoplasms/drug therapy/genetics
MH  - RNA, Circular/*pharmacology
MH  - Real-Time Polymerase Chain Reaction/methods
MH  - Signal Transduction/*drug effects
MH  - Vascular Endothelial Growth Factor A/*drug effects
MH  - Vascular Endothelial Growth Factor Receptor-2/*drug effects
PMC - PMC8880967
COIS- Conflict of interest: The authors have no conflicts of interest to declare.
EDAT- 2021/07/19 06:00
MHDA- 2022/03/12 06:00
PMCR- 2021/07/01
CRDT- 2021/07/18 20:56
PHST- 2021/07/18 20:56 [entrez]
PHST- 2021/07/19 06:00 [pubmed]
PHST- 2022/03/12 06:00 [medline]
PHST- 2021/07/01 00:00 [pmc-release]
AID - bmj-38-4-229 [pii]
AID - 10.5152/balkanmedj.2021.21145 [doi]
PST - ppublish
SO  - Balkan Med J. 2021 Jul;38(4):229-238. doi: 10.5152/balkanmedj.2021.21145.