LingLing Wang,1,* Li Liang,2,* Jing Qian,3 Chao Yu,1 Yu Shi,3 XiaoDi Yan,3 Xiang Chen1 

1Department of Clinical Laboratory, Nantong First People’s Hospital, Nantong City, Jiangsu Province, 226000, People’s Republic of China; 2Department of Interventional, Nantong First People’s Hospital, Nantong City, Jiangsu Province, 226000, People’s Republic of China; 3Department of Tumor Radiotherapy, Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province, 226001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiang Chen, Department of Inspection, Nantong First People’s Hospital, No. 666, Shengli Road, Guanyinshan Street, Chongchuan District, Nantong City, Jiangsu Province, 226000, People’s Republic of China, Email chenxiang_CXCH@hotmail.com

Objective: This study aimed to investigate the expression and functional role of hsa_circ_0007991 in hepatocellular carcinoma (HCC).
Methods: RNA expression data of HCC and corresponding non-tumor liver tissues were obtained from the GEO database, and differential expression analysis was conducted to identify significantly dysregulated circRNAs. A total of 68 clinical samples from HCC patients were collected, and hsa_circ_0007991 level was quantified using RT-qPCR. Gain- and loss-of-function experiments were performed on HCC cells, followed by assessments of cellular proliferation, apoptosis, and immune evasion using CCK-8, EdU incorporation assays, flow cytometry, and ELISA. The role of hsa_circ_0007991 as a ceRNA was further validated using dual-luciferase reporter assay, RNA immunoprecipitation, and nuclear-cytoplasmic fractionation.
Results: A significant upregulation of hsa_circ_0007991 was observed in HCC tissues, with increased levels correlating with advanced TNM stages. hsa_circ_0007991 silencing significantly suppressed HCC cell proliferation and immune evasion, while promoting apoptosis, whereas hsa_circ_0007991 overexpression yielded the opposite effects. The function of hsa_circ_0007991 involves binding to miR-505-3p, which modulates the expression of calnexin (CANX), influencing the biological behaviors of HCC cells. Rescue experiments validated the essential function of the hsa_circ_0007991/miR-505-3p/CANX pathway in HCC.
Conclusion: hsa_circ_0007991 is upregulated in HCC and closely associated with tumor proliferation and immune evasion by regulating the miR-505-3p/CANX axis.

Keywords: hepatocellular carcinoma, hsa_circ_0007991, proliferation, immune evasion