Potential therapies for residual hepatoblastoma following incomplete ablation treatment in a nude mouse subcutaneous xenograft model based on lncRNA and mRNA expression profiles

基于lncRNA和mRNA表达谱的裸鼠皮下异种移植模型中不完全消融治疗后残留肝母细胞瘤的潜在治疗方法

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作者:Xiao-Dong Wang # ,Jin-Bo Peng # ,Chuan-Yang Zhou ,Qiao Que ,Hai-Yuan Li ,Yun He ,Hong Yang

Abstract

Tumor recurrence following radiofrequency ablation (RFA) treatment in liver cancer is an important factor affecting patient prognosis. Furthermore, the biological role of long non‑coding RNAs (lncRNAs) in residual hepatoblastoma (HB) tissues after RFA remains largely unknown. By using microarray technology, this study investigated the expression of lncRNAs and mRNAs among four pairs of HB tissues (incomplete ablation treatment and no treatment) in a nude mouse subcutaneous xenograft model. Subsequently, bioinformatics analysis was used to understand the functions and pathways of the identified mRNAs. Finally, a connectivity map (CMap) analysis was conducted to identify potential therapeutic strategies for residual HB tissues. Compared with the untreated nude mouse subcutaneous xenograft model, in the experimental group, a significant difference in the expression of 740 lncRNAs and 663 mRNAs was detected. Subsequently, bioinformatics analysis revealed that the differentially expressed mRNAs were significantly enriched in pathways associated with antigen processing, the presentation of endogenous antigens, the regulation of cellular metabolic processes, MAPK signaling and cell cycle regulation. Additionally, six compounds (valproic acid, metformin, tanespimycin, wortmannin, fulvestrant and MK‑886) were identified by CMap analysis as potential therapeutic agents for the treatment of residual HB tissues. These findings provide a novel insight into the pathogenesis of residual HB and potential therapeutic strategies for aggressive tumor recurrence following RFA treatment in patients with HB. Keywords: long non-coding RNA; hepatoblastoma; radiofrequency ablation; connectivity map.

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