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Circ‐SPECC1 modulates TGFβ2 and autophagy under oxidative stress by sponging miR‐33a to promote hepatocellular carcinoma tumorigenesis

Circular RNAs (circRNAs) play vital roles in the pathogenesis and development of multiple cancers, including hepatocellular carcinoma (HCC). Nevertheless, the regulatory mechanisms of circ‐SPECC1 in HCC remain poorly understood. In our study, we found that circ‐SPECC1 was apparently downregulated in...

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Detalles Bibliográficos
Autores principales: Zhang, Bin, Liu, Zhiyi, Cao, Kuan, Shan, Wengang, Liu, Jin, Wen, Quan, Wang, Renhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433841/
https://www.ncbi.nlm.nih.gov/pubmed/32627938
http://dx.doi.org/10.1002/cam4.3219
Descripción
Sumario:Circular RNAs (circRNAs) play vital roles in the pathogenesis and development of multiple cancers, including hepatocellular carcinoma (HCC). Nevertheless, the regulatory mechanisms of circ‐SPECC1 in HCC remain poorly understood. In our study, we found that circ‐SPECC1 was apparently downregulated in H(2)O(2)‐treated HCC cells. Additionally, knockdown of circ‐SPECC1 inhibited cell proliferation and promoted cell apoptosis of HCC cells under H(2)O(2) treatment. Moreover, circ‐SPECC1 inhibited miR‐33a expression by direct interaction, and miR‐33a inhibitor partially reversed the effect of circ‐SPECC1 knockdown on proliferation and apoptosis of H(2)O(2)‐treated HCC cells. Furthermore, TGFβ2 was demonstrated to be a target gene of miR‐33a and TGFβ2 overexpression rescued the phenotypes of HCC cells attenuated by miR‐33a mimics. Meanwhile, autophagy inhibition by 3‐methyladenine (3‐MA) abrogated the effect of miR‐33a mimics on proliferation and apoptosis of H(2)O(2)‐treated HCC cells. Finally, knockdown of circ‐SPECC1 hindered tumor growth in vivo. In conclusion, our study demonstrated that circ‐SPECC1 regulated TGFβ2 and autophagy to promote HCC tumorigenesis under oxidative stress via miR‐33a. These findings might provide potential treatment strategies for patients with HCC.