m6A modification of circHPS5 and hepatocellular carcinoma progression through HMGA2 expression

• Main Authors: Dawei Rong, Fan Wu, Chen Lu, Guangshun Sun, Xiaoli Shi, Xiaoyuan Chen, Yongjiu Dai, Weizhe Zhong, Xiaopei Hao, Jinren Zhou, Yongxiang Xia, Weiwei Tang, Xuehao Wang
• Format: Article
• Language: English
• Published: Elsevier 2021-12-01
• Series: Molecular Therapy: Nucleic Acids
• Subjects: m6A modification; circRNA; hepatocellular carcinoma; epithelial-mesenchymal transition; circHPS5; HMGA2
• Online Access: http://www.sciencedirect.com/science/article/pii/S2162253121002304

N6-methyladenosine (m6A) is capable of mediating circRNA generation in carcinoma biology. Nevertheless, the posttranscriptional systems of m6A and circRNA in hepatocellular carcinoma (HCC) development are still unclear. The present study identified a circRNA with m6A modification, circHPS5, which was increased in neoplasm HCC tissues and indicated poor patient survival. Silencing of circHPS5 inhibited epithelial-mesenchymal transition (EMT) and cancer stem-like cell (CSC) phenotypes. Notably, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. In addition, we demonstrated that circHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate HCC cell tumorigenesis. Accordingly, the m6A modification of circHPS5 was found to modulate cytoplasmic output and increase HMGA2 expression to facilitate HCC development. The new regulatory model of “circHPS5-HMGA2” provides a new perspective for circHPS5 as an important prognostic marker and therapeutic target in HCC and provides mechanistic insight for exploring the carcinogenic mechanism of circHPS5 in HCC.