Int J Biol Sci 2019; 15(5):1091-1103. doi:10.7150/ijbs.31533
Circular RNA CircCACTIN Promotes Gastric Cancer Progression by Sponging MiR-331-3p and Regulating TGFBR1 Expression
1. Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
2. Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
3. Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
4. Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Background: Circular RNAs (circRNAs) are a new class of RNAs that play a significant role in regulating gene expression and biological function. However, the expression profile and function of circRNAs in gastric cancer (GC) remain mostly uncertain. In the present study, we researched the expression profile of circRNAs in human GC tissues and explored the role of circCACTIN (hsa_circ_0092303).
Methods: Circular RNA microarray assays were performed to detect circular RNA expression profiles of GC and circCACTIN was identified for further investigation. Quantitative real-time PCR was used to detect the expression of circCACTIN, miR-331-3p and TGFBR1 in GC specimens and cell lines. CircCACTIN was stably silenced and overexpressed in GC cells, and cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), as well as tumorigenesis in nude mice were performed to assess the effect of circCACTIN on GC.
Results: CircCACTIN expression was obviously up-regulated in GC tissues and cell lines. Knockdown of circCACTIN inhibited GC cells proliferation, migration, invasion and EMT. Enforced-expression of circCACTIN promoted GC cells migration, invasion and EMT, but had no effect on GC cells proliferation. Moreover, in vivo experiments, circCACTIN up-regulation promoted GC tumor growth and EMT, and circCACTIN down-regulation inhibited GC tumor growth and EMT. Binding interactions were detected between circCACTIN and miR-331-3p, and between miR-331-3p and TGFBR1 by Dual-luciferase reporter assays. Mechanistically, we demonstrated that circCACTIN promoted gastric cancer progression by sponging miRNA-331-3p and regulating TGFBR1 mRNA expression.
Conclusion: The circCACTIN/miR-331-3p/TGFBR1 axis affected the proliferation, migration, invasion and EMT of GC through the mechanism of competing endogenous RNAs (ceRNA). Furthermore, our results identified circCACTIN as a novel oncogenic circRNA in GC.
Keywords: circCACTIN, gastric cancer, progression, miR-331-3p, TGFBR1
Zhang L, Song X, Chen X, Wang Q, Zheng X, Wu C, Jiang J. Circular RNA CircCACTIN Promotes Gastric Cancer Progression by Sponging MiR-331-3p and Regulating TGFBR1 Expression. Int J Biol Sci 2019; 15(5):1091-1103. doi:10.7150/ijbs.31533. Available from http://www.ijbs.com/v15p1091.htm