Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis

Autor: Quanbo Zhou, Xiaofeng Guo, Leyi Huang, Decan Jiang, Dan Su, Zhiguo Li, Rufu Chen, Yuming Luo, Changhao Chen, Zhiqiang Fu, Yao Kong, Zhihua Li
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
endocrine system diseases
Apoptosis
Mice
SCID
Biology
medicine.disease_cause
lcsh:RC254-282
Metastasis
Pancreatic ductal adenocarcinoma
03 medical and health sciences
Mice
0302 clinical medicine
microRNA
medicine
Biomarkers
Tumor
Tumor Cells
Cultured
Animals
Humans
circBFAR
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
Gene knockdown
Akt/PKB signaling pathway
Research
RNA
Circular
Proto-Oncogene Proteins c-met
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Xenograft Model Antitumor Assays
digestive system diseases
Gene Expression Regulation
Neoplastic
Pancreatic Neoplasms
MicroRNAs
030104 developmental biology
Oncology
PI3K/Akt pathway
030220 oncology & carcinogenesis
Cancer research
MET
Molecular Medicine
Ectopic expression
miR-34b-5p
Carcinogenesis
Proto-Oncogene Proteins c-akt
Carcinoma
Pancreatic Ductal
Zdroj: Molecular Cancer
Molecular Cancer, Vol 19, Iss 1, Pp 1-18 (2020)
ISSN: 1476-4598
Popis: Background Accumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression. However, the biological processes and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. Method CircRNAs were verified by Sanger sequencing. Colony formation, 5-Ethynyl-2′-deoxyuridine (EdU), and Transwell assays were performed to investigate the effect of circBFAR on the proliferation, invasion, and migration of PDAC cells in vitro. RNA pull-down assays were conducted to verify the binding of circBFAR with microRNA miR-34b-5p. Results In the present study, we identified a novel circRNA (termed as circBFAR, hsa_circ_0009065) that was upregulated in a 208-case cohort of patients with PDAC. The ectopic expression of circBFAR correlated positively with the tumor-node-metastasis (TNM) stage and was related to poorer prognosis of patients with PDAC. Moreover, circBFAR knockdown dramatically inhibited the proliferation and motility of PDAC cells in vitro and their tumor-promoting and metastasis properties in in vivo models. Mechanistically, circBFAR upregulated mesenchymal-epithelial transition factor (MET) expression via sponging miR-34b-5p. Additionally, circBFAR overexpression increased the expression of MET and activated downstream phosphorylation of Akt (Ser 473) and further activated the MET/PI3K/Akt signaling pathway, which ultimately promoted the progression of PDAC cells. Importantly, application of MET inhibitors could significantly attenuate circBFAR-mediated tumorigenesis in vivo. Conclusions Our findings showed that circBFAR plays an important role in the proliferation and metastasis of PDAC, which might be explored as a potential prognostic marker and therapeutic target for PDAC.
Databáze: OpenAIRE
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