E2F3 promotes liver cancer progression under the regulation of circ-PRKAR1B

• Published in: Molecular therapy. Nucleic acids Vol. 26; pp. 104 - 113
• Main Authors: Liu, Guodong, Ouyang, Xiwu, Gong, Liansheng, Yao, Lei, Liu, Shiqing, Li, Jiarong, Zhang, Qi, Xiao, Yao
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 03.12.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: circ-PRKAR1B; E2F3; invasion; liver cancer; migration; miRNAs; Original; migration; liver cancer; E2F3; miRNAs; invasion; circ-PRKAR1B
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2021.07.002

Liver cancer is one of the most lethal malignant tumors in the world. The high recurrence and mortality rate make it urgent for scientists and clinicians to find new targets for better treatment of liver cancer. Here, we found that circ-PRKAR1B expression was increased in the paired intrahepatic metastasis sample through high-throughput sequencing. Further experiments also confirmed its high expression both in carcinoma and metastasis when compared to the paired para-carcinoma and the paired carcinoma, respectively. Mechanism study showed that circ-PRKAR1B could promote liver cancer progression through the miR-432-5p/E2F3 pathway, and microRNA-432-5p could directly target the 3′ untranslated region (UTR) of E2F3 mRNA to suppress its translation, thereby influencing liver cancer cell invasion and migration capacities. Clinical data obtained by using online databases based on The Cancer Genome Atlas (TCGA) samples and the clinicopathological data of liver cancer patients who underwent surgery in our hospital in the past 2 years also confirmed the significance of circ-PRKAR1B/miR-432-5p/E2F3 signaling in liver cancer progression. Animal experiments also indicated that targeting this newly identified signaling by overexpressing microRNA-432-5p could suppress the progression of liver cancer. Together, our study suggests that circ-PRKAR1B plays an important role in the regulation of liver cancer progression, and targeting this new circ-PRKAR1B/miR-432-5p/E2F3 signaling may help us find new treatment strategies to better suppress liver cancer progression. [Display omitted] High recurrence and mortality require clinicians to find new targets to better treat liver cancer. The study of Xiao et al. defined the role of circ-PRKAR1B in liver cancer progression through miR-432-5p/E2F3 signaling and builds a rationale to develop the signaling targeted therapies for better treatment of liver cancer.