Circ-0005105 activates COL11A1 by targeting miR-20a-3p to promote pancreatic ductal adenocarcinoma progression

• Published in: Cell death & disease Vol. 12; no. 7; p. 656
• Main Authors: Ma, Gang, Li, Guichen, Fan, Wufeng, Xu, Yuanhong, Song, Shaowei, Guo, Kejian, Liu, Zhe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.06.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/105; 13/89; 38/1; 38/109; 38/47; 38/61; 631/67/1504/1713; 631/80/84/2336; 64/60; Adenocarcinoma; Animals; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - secondary; Cell Biology; Cell Culture; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Collagen; Collagen Type XI - genetics; Collagen Type XI - metabolism; Databases, Genetic; Disease Progression; Epithelial-Mesenchymal Transition; Experiments; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Hybridization; Immunology; Immunoprecipitation; Life Sciences; Localization; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Medical prognosis; Mesenchyme; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neoplasm Invasiveness; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pathogenesis; Phenotypes; Polymerase chain reaction; Prognosis; Reverse transcription; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction; Tumorigenesis; Tumorigenicity
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03938-8

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.