TUG1 Promoted Tumor Progression by Sponging miR-335-5p and Regulating CXCR4-Mediated Infiltration of Pro-Tumor Immunocytes in CTNNB1-Mutated Hepatoblastoma

Fujing Xie,1,* Lianhai Zhang,2,* Qing Yao,3 Liyu Shan,3 Jike Liu,2 Nanhai Dong,4 Jun Liang1 1Department of Pediatrics, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, People’s Republic of China; 2Department of Pediatric Surgery, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, People’s Republic of China; 3Medical College of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, People’s Republic of China; 4Department of Clinical Laboratory, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Liang; Nanhai Dong West Dongchang Road 67, Liaocheng 252000, People’s Republic of ChinaTel +86 13346255358; +86 13563016897Email 251217955@qq.com; dnhjyk@163.comIntroduction: HB presents with the highest frequency of CTNNB1 mutations, resulting in activation of Wnt signaling pathway. A number of studies have demonstrated CTNNB1 mutation contributed to the development of HB. However, limited research explored the function of lncRNAs in HB with CTNNB1 mutation.Methods: We screened lncRNA expression profiles in CTNNB1-mutated HB samples and identified lncRNAs associated with malignant phenotype in HB. The association between lncRNA and immune microenvironment was investigated. The biological function of lncRNA was further explored using in vitro experiments.Results: TUG1 was identified as onco-lncRNA in CTNNB1-mutated HB. TUG1 was shown to be associated with the infiltration of pro-tumor immunocytes via regulating the expression of CXCR4, a chemokine receptor playing a critical role in regulation of immune microenvironment. Inhibiting TUG1 could increase endogenous levels of miR-335-5p and consequently downregulating CXCR4, a direct target of miR-335-5p.Conclusion: Our findings provide evidence for TUG1 mediating infiltration of pro-tumor immunocytes in HB patients carrying CTNNB1 mutation. TUG1-miR-335-5p-CXCR4 axis might be a promising immunological target for the treatment of HB patients.Keywords: hepatoblastoma, TUG1, CXCR4, immunocyte