Circ-0005105 activates COL11A1 by targeting miR-20a-3p to promote pancreatic ductal adenocarcinoma progression
| Autor: | Yuanhong Xu, Zhe Liu, Wu-Feng Fan, Shaowei Song, Gang Ma, Guichen Li, Kejian Guo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition Lung Neoplasms Immunology Cell Mice Nude Biology medicine.disease_cause Collagen Type XI Article Metastasis 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Cell Movement Cell Line Tumor microRNA Databases Genetic medicine Gene silencing Animals Humans Neoplasm Invasiveness Cell Proliferation Mice Inbred BALB C QH573-671 Competing endogenous RNA Cell Biology Pancreatic cancer RNA Circular medicine.disease Collagen type XI alpha 1 Cell invasion Gene Expression Regulation Neoplastic Pancreatic Neoplasms MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Disease Progression Carcinogenesis Cytology Carcinoma Pancreatic Ductal Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 12, Iss 7, Pp 1-12 (2021) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Growing evidence indicates that circular RNAs (circRNAs) are closely involved in tumorigenesis, but the association between circRNAs and pancreatic ductal adenocarcinoma (PDAC) is far from clear. Here, we focused on the functional investigation of circ-0005105, a newly identified circRNA, in PDAC progression. In the present study, we assessed circ-0005105 expression in PDAC tissues and cell lines with quantitative reverse transcription–polymerase chain reaction (qRT-PCR). The biological functions of circ-0005105 in cellular proliferation and invasion were identified through gain- and loss-of-function experiments in vitro and in vivo. The interaction between circ-0005105 and the microRNA (miR)-20a-3p–COL11A1 (collagen type XI alpha 1) axis was examined using luciferase reporter and RNA immunoprecipitation assays. We found that circ-0005105 expression was upregulated in both PDAC tissues and cell lines. Higher circ-0005105 expression correlated positively with the malignant clinical phenotype and poor prognosis of patients with PDAC. Gain- and loss-of-function analysis showed that circ-0005105 facilitated both in vitro and in vivo cellular proliferation and invasion. Mechanistically, circ-000510 served as a competing endogenous RNA (ceRNA) of miR-20a-3p and indirectly modulated COL11A1 expression, leading to activation of epithelial–mesenchymal transition (EMT). Rescue experiments suggested that the oncogenic activity of circ-0005105 was dependent on the modulation of the miR-20a-3p–COL11A1 axis. More importantly, COL11A1 overexpression was significantly associated with poor prognosis in PDAC, and silencing COL11A1 reduced PDAC cell tumorigenicity and metastasis. Taken together, our findings confirm for the first time that circ-0005105 has critical functions by regulating the miR-20a-3p–COL11A1 axis. In the clinic, circ-0005105 can act as a potential prognostic marker and therapeutic target in PDAC. |
| Databáze: | OpenAIRE |
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