Cancer Management and Research (Jan 2021)
Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis
Abstract
Wei Fan,1,* Lei Chen,2,* Xiaojuan Wu,3 Tong Zhang4 1Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Shandong First Medical University (The Forth People’s Hospital of Jinan), Jinan 250031, Shandong, People’s Republic of China; 2Department of Emergency Medicine, Xiang’an Hospital of Xiamen University, Xiamen 361101, Fujian, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan, People’s Republic of China; 4Department of Hepatobiliary Surgery, Xinghua City People’s Hospital, Xinghua 225700, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tong ZhangDepartment of Hepatobiliary Surgery, Xinghua City People’s Hospital, No. 4 Jianxing Garden, Zhangyang North Village, Xinghua 225700, Jiangsu, People’s Republic of ChinaEmail [email protected]: Circular RNAs (circRNAs) have been implicated in the progression and chemoresistance development of hepatocellular carcinoma (HCC). However, the precise parts of circ_0031242 in HCC chemoresistance are still not fully understood.Methods: The levels of circ_0031242, miR-924 and POU class 3 homeobox 2 (POU3F2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay or Western blot analysis. IC50 value for cisplatin (DDP) and cell viability were measured by the cell counting kit-8 (CCK-8) assay. Cell migration, invasion and apoptosis were assessed by transwell assay and flow cytometry, respectively. Targeted correlations among circ_0031242, miR-924 and POU3F2 were verified by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.Results: Our data revealed that circ_0031242 was associated with HCC resistance to DDP. The silencing of circ_0031242 diminished DDP resistance, suppressed cell viability, migration, invasion and promoted apoptosis of DDP-resistant HCC cells (Huh7-R and SNU-387-R) in vitro, as well as enhanced DDP sensitivity in vivo. Mechanistically, circ_0031242 directly interacted with miR-924 by binding to miR-924. Moreover, miR-924 was a downstream effector of circ_0031242 function. POU3F2 was a direct target of miR-924, and miR-924 overexpression regulated DDP-resistant HCC cell progression and DDP resistance by down-regulating POU3F2. Furthermore, circ_0031242 modulated POU3F2 expression through sponging miR-924.Conclusion: Our findings identified that circ_0031242 functioned as an important regulator in DDP-resistant HCC cell progression and DDP resistance through the miR-924/POU3F2 axis, illuminating circ_0031242 as a potential therapeutic target for the chemoresistant HCC.Keywords: HCC, chemoresistance, circ_0031242, miR-924, POU3F2
