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

Abstract

Introduction: 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.

MiR‐622 acts as a tumor suppressor to induce cell apoptosis and inhibit metastasis in human prostate cancer

“…miR‐622 is regulated by the enhancer of zeste homolog 2 (EZH2), which causes the down‐regulation of miR‐622 through the H3K27 trimethylation methylation‐related silencing of the promoter in hepatocellular carcinoma. In accordance with these data, Xie et al reported that up‐regulation of miR‐335 led to reduced expression of CXCR‐4 in HepG2 cells (Xie et al., 2020).…”

Neuropilin-2 Is Associated With Increased Hepatoblastoma Cell Viability and Motility

“…In breast cancer cells, neutralizing NRP2 antibody blocked cytoplasmic C-X-C Motif Chemokine Receptor 4 ( CXCR4 ) expression which was followed by decreased tumor cell migration ( 22 ). Interestingly, upregulation of CXCR4 was recently associated with the infiltration of pro-tumorigenic macrophages, neutrophils, and dendritic cells in HB tissue samples ( 58 ). Considering the NRP2-CXCR4 axis, NRP2 targeting might attenuate the growth of HB at multiple levels.…”

Functions and Targets of miR-335 in Cancer

“… 71 By sponging miR-335 and regulating CXC chemokine receptor 4 (CXCR4), lncRNA TUG1 promotes tumor progression in CTNNB1-mutated hepatoblastoma. 111 LncRNA RP11-436H11.5, functioning as an endogenous sponge for miR-335, upregulates BCL-W by sponging miR-335 and promotes proliferation and invasion in RCC. 60 In bladder cancer, lncRNA SLCO4A1-AS1 promotes proliferation and migration by regulating the miR-335/OCT4 axis.…”