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Circ-OXCT1 Suppresses Gastric Cancer EMT and Metastasis by Attenuating TGF-β Pathway Through the Circ-OXCT1/miR-136/SMAD4 Axis.
- Source :
-
OncoTargets & Therapy . May2020, Vol. 13, p3987-3998. 12p. - Publication Year :
- 2020
-
Abstract
- Background: Circular RNAs (circRNAs) have been proven to play important roles in tumorigenesis. However, the mechanism by which circRNAs act on gastric cancer (GC) through epithelial-to-mesenchymal transition (EMT) is unclear. In this study, we identified circ-OXCT1 and elucidated its function on EMT in GC. Methods: Tissue circRNA microarray analysis and qRT-PCR were utilized to determine the expression level of circ-OXCT1 in GC. Luciferase reporter assay and FISH were employed to confirm the interaction between circ-OXCT1 and miR-136. CCK-8, cloning formation, transwell, wound healing, nude mice experiment, circ-OXCT1 overexpression and silencing were conducted to elucidate the function of circ-OXCT1 in vivo and in vitro. Western blot and rescue experiment were carried out to evaluate the changes of EMT-related proteins induced by circ-OXCT1 overexpression or silencing. Results: Circ-OXCT1 was downregulated in GC tissues and cell lines. Its expression level was significantly associated with lymph node metastasis, pathologic stage and overall survival rate through clinicopathologic data analysis. Circ-OXCT1 silencing downregulated SMAD4 expression and accordingly regulated expression of E-cadherin, N-cadherin and vimentin through the transforming growth factor-beta (TGF-β)/Smad signaling pathway by a circ-OXCT1/miR-136/SMAD4 axis, resulting in enhancement of EMT and subsequent boost of cell migration, invasion and nude mice lung metastasis. Conclusion: Our data showed that circ-OXCT1 suppresses gastric cancer EMT and metastasis through TGF-β/Smad signaling pathway. The clinicopathologic data analysis revealed that circ-OXCT1 overexpression could be a novel treatment for advanced GC especially with distant metastasis by targeting the circ-OXCT1/miR-136/SMAD4 axis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *STOMACH cancer
*METASTASIS
*CIRCULAR RNA
*CELL migration
*CELL lines
Subjects
Details
- Language :
- English
- ISSN :
- 11786930
- Volume :
- 13
- Database :
- Academic Search Index
- Journal :
- OncoTargets & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 143760423
- Full Text :
- https://doi.org/10.2147/OTT.S239789