Circular RNA UBE2Q2 promotes malignant progression of gastric cancer by regulating signal transducer and activator of transcription 3-mediated autophagy and glycolysis

• Published in: Cell death & disease Vol. 12; no. 10; p. 910
• Main Authors: Yang, Jing, Zhang, Xing, Cao, Jiacheng, Xu, Penghui, Chen, Zetian, Wang, Sen, Li, Bowen, Zhang, Lu, Xie, Li, Fang, Lang, Xu, Zekuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.10.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 14/63; 631/67/1504/1829; 64/60; 692/699/67/1504/1829; Animals; Antibodies; Autophagosomes - metabolism; Autophagosomes - ultrastructure; Autophagy; Autophagy - genetics; Base Sequence; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Circular RNA; Disease Progression; Epithelial-Mesenchymal Transition - genetics; Exosomes - metabolism; Exosomes - ultrastructure; Female; Gastric cancer; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Glycolysis; Glycolysis - genetics; Humans; Immunology; Life Sciences; Male; Metastases; Metastasis; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Phagocytosis; RNA, Circular - genetics; RNA, Circular - metabolism; RNA-binding protein; Stat3 protein; STAT3 Transcription Factor - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Transcription; Tumor Burden; Tumorigenicity
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04216-3

Gastric cancer remains the third leading cause of cancer-related mortality worldwide. Emerging evidence has shown that circular RNAs (circRNAs) play a critical regulatory role in the occurrence and development of various cancers through sponging miRNAs or acting as RNA-binding protein (RBP) sponges. We found that circUBE2Q2 was significantly upregulated in GC tissues and cell lines. Knockdown of circUBE2Q2 inhibited proliferation, migration, invasion, and glycolysis, and increased autophagy in vitro. In addition, knockdown of circUBE2Q2 inhibited GC tumorigenicity and metastasis potential in vivo. A series of experiments were performed to confirm that circUBE2Q2 regulates GC progression via the circUBE2Q2-miR-370-3p- STAT3 axis and promotes tumor metastasis through exosomal communication. Further in vivo experiments confirmed that, combination treatment of circUBE2Q2 knocking down and STAT3 inhibitor has synergistic effects on the gastric cancer growth inhibition, which provides a possibility to enhance the sensitivity of targeted drugs to gastric cancer through targeting circUBE2Q2. Our findings revealed that circUBE2Q2 may serve as a new proliferation-promoting factor and prognostic marker in gastric cancer.