PMID- 35517414
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1837-9664 (Print)
IS  - 1837-9664 (Electronic)
IS  - 1837-9664 (Linking)
VI  - 13
IP  - 7
DP  - 2022
TI  - CAV2 Regulates Mir-4723/Wnt7A Signalling Axis through Endocytosis and 
      Epithelial-Mesenchymal Transition to Promote Proliferation, Invasion, and 
      Metastasis of Pancreatic Cancer Cells.
PG  - 2200-2212
LID - 10.7150/jca.69617 [doi]
AB  - Background: Pancreatic cancer is one of the most aggressive malignancies 
      globally, with no improvement in the cure rates yet.Caveolin-2 (CAV2) has been 
      repeatedly reported to play an important role in cellular transport and 
      signalling and in exhibiting a pro-oncogenic response in a variety of tumours, 
      although its specific action mechanisms in pancreatic cancer are not well 
      documented. MiRNA is recognized as a therapeutic target for a variety of tumours, 
      making it an important regulator of the Wnt/beta-catenin signalling pathway. 
      MiR-4723/Wnt7A constitutes an oncogenic signalling axis in pancreatic cancer by 
      targeting and inhibiting Wnt7A through the activation of MiR4723, but its 
      molecular action mechanism remains unexplored. Therefore, in the present study, 
      we investigated the effect of CAV2 on the MiR-4723/Wnt7A pathway and its action 
      mechanism. Methods: We employed TCGA, the GEO database for bioinformatics 
      analysis, cell proliferation assay, wound healing assay, Transwell assay, 
      colony-forming assay, qRT-PCR, and Western blotting to validate the 
      cancer-promoting role of CAV2 in pancreatic cancer and to determine its potential 
      target WNT7A. We then explored CAV2 as a positive regulator of the 
      Wnt7A/beta-catenin pathway through immunofluorescence assay, qRT-PCR, and Western 
      blotting. Database analyses, CCK-8 and qRT-PCR revealed that MiR-4723 is an 
      oncogene in pancreatic cancer. Luciferase assay and qRT-PCR revealed that 
      MiR-4723 is a negative regulator of the Wnt7A/beta-catenin pathway. To investigate 
      the mechanism of CAV2 action on MiR-4723/Wnt7A, we detected the gene expression 
      of CAV2 through qRT-PCR after MiR-4723 overexpression. Several genes related to 
      endocytosis and epithelial-mesenchymal transition (EMT) were subsequently 
      analysed through immunofluorescence, Western blotting, and qRT-PCR. Results: 
      Overexpression of CAV2 promotes invasion, migration, cloning and metastasis of 
      pancreatic cancer cells. Overexpression of MiR-4723 inhibits CAV2 expression. 
      Here, we are the first to demonstrate that CAV2 exerts a pro-carcinogenic effect 
      on pancreatic cancer through the activation of the Wnt7A/beta-catenin signalling 
      pathway. Conclusion: CAV2 can regulate the MiR-4723/Wnt7A signalling axis in 
      pancreatic cancer cell lines by inhibiting endocytosis and promoting EMT, thereby 
      fulfilling the mechanism pro-carcinogenic effects.
CI  - (c) The author(s).
FAU - Li, Dan
AU  - Li D
AD  - Key Laboratory of Hepatobiliary and Pancreatic Surgery and Guizhou Medical 
      University, Guiyang, China.
FAU - Guo, Yuting
AU  - Guo Y
AD  - Key Laboratory of Hepatobiliary and Pancreatic Surgery and Guizhou Medical 
      University, Guiyang, China.
AD  - Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of 
      Guizhou Medical University, Guiyang, China.
FAU - Tian, She
AU  - Tian S
AD  - Key Laboratory of Hepatobiliary and Pancreatic Surgery and Guizhou Medical 
      University, Guiyang, China.
AD  - Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of 
      Guizhou Medical University, Guiyang, China.
FAU - Zhu, Changhao
AU  - Zhu C
AD  - Key Laboratory of Hepatobiliary and Pancreatic Surgery and Guizhou Medical 
      University, Guiyang, China.
AD  - Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of 
      Guizhou Medical University, Guiyang, China.
FAU - Sun, Chengyi
AU  - Sun C
AD  - Key Laboratory of Hepatobiliary and Pancreatic Surgery and Guizhou Medical 
      University, Guiyang, China.
AD  - Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of 
      Guizhou Medical University, Guiyang, China.
LA  - eng
PT  - Journal Article
DEP - 20220404
PL  - Australia
TA  - J Cancer
JT  - Journal of Cancer
JID - 101535920
PMC - PMC9066196
OTO - NOTNLM
OT  - Caveolin-2
OT  - Endocytosis
OT  - MiR-4723
OT  - Pancreatic cancer
OT  - WNT7A
OT  - Wnt/beta-catenin pathway
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/05/07 06:00
MHDA- 2022/05/07 06:01
PMCR- 2022/01/01
CRDT- 2022/05/06 05:49
PHST- 2021/11/30 00:00 [received]
PHST- 2022/03/11 00:00 [accepted]
PHST- 2022/05/06 05:49 [entrez]
PHST- 2022/05/07 06:00 [pubmed]
PHST- 2022/05/07 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - jcav13p2200 [pii]
AID - 10.7150/jca.69617 [doi]
PST - epublish
SO  - J Cancer. 2022 Apr 4;13(7):2200-2212. doi: 10.7150/jca.69617. eCollection 2022.