Molecular cancer, 2020-05, Vol.19 (1), p.82-82, Article 82
2020
Details
- Autor(en) / Beteiligte
- Titel
- circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer
- Ist Teil von
- Molecular cancer, 2020-05, Vol.19 (1), p.82-82, Article 82
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Patients with lymph node (LN)-positive pancreatic ductal adenocarcinoma (PDAC) have extremely poor survival rates. Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNAs, have been proposed to mediate the progression of diverse types of tumors. However, the role and underlying regulatory mechanisms of circRNAs in the LN metastasis of PDAC remain unknown. Next-generation sequencing was used to identify differentially expressed circRNAs between PDAC and normal adjacent tissues. In vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1. RNA pulldown and luciferase assays were performed to examine the binding of circNFIB1 and miR-486-5p. In the present study, we identified that a novel circRNA (circNFIB1, hsa_circ_0086375) was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients. Functionally, circNFIB1 knockdown promoted lymphangiogenesis and LN metastasis of PDAC both in vitro and in vivo. Mechanistically, circNFIB1 functioned as a sponge of miR-486-5p, and partially reversed the effect of miR-486-5p. Moreover, circNFIB1 attenuated the oncogenic effect of miR-486-5p and consequently upregulated PIK3R1 expression, which further downregulated VEGF-C expression through inhibition of the PI3K/Akt pathway, and ultimately suppressed lymphangiogenesis and LN metastasis in PDAC. Our findings provide novel insight into the underlying mechanism of circRNA-mediated LN metastasis of PDAC and suggest that circNFIB1 may serve as a potential therapeutic target for LN metastasis in PDAC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1476-4598eISSN: 1476-4598DOI: 10.1186/s12943-020-01205-6Titel-ID: cdi_doaj_primary_oai_doaj_org_article_85af6f744c7a467880526cc8085ab129
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, Adenocarcinoma, AKT protein, Animals, Apoptosis, Biomarkers, Tumor - genetics, Biomarkers, Tumor - metabolism, Cancer, Cancer metastasis, Carcinoma, Pancreatic Ductal - genetics, Carcinoma, Pancreatic Ductal - metabolism, Carcinoma, Pancreatic Ductal - pathology, Cell Proliferation, circNFIB1, Class Ia Phosphatidylinositol 3-Kinase - genetics, Class Ia Phosphatidylinositol 3-Kinase - metabolism, Development and progression, Female, Gene Expression Regulation, Neoplastic, Humans, Lymph nodes, Lymphangiogenesis, Lymphatic Metastasis, Lymphatic system, Medical prognosis, Metastases, Metastasis, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs, MicroRNAs - genetics, Next-generation sequencing, NFI Transcription Factors - genetics, Pancreatic cancer, Pancreatic Neoplasms - genetics, Pancreatic Neoplasms - metabolism, Pancreatic Neoplasms - pathology, PI3K/Akt signaling pathway, PIK3R1, Prognosis, Ribonucleic acid, RNA, RNA, Circular - genetics, Therapeutic applications, Tumor Cells, Cultured, Tumors, Vascular endothelial growth factor, Vascular Endothelial Growth Factor C - genetics, Vascular Endothelial Growth Factor C - metabolism, Xenograft Model Antitumor Assays