Potential therapies for residual hepatoblastoma following incomplete ablation treatment in a nude mouse subcutaneous xenograft model based on lncRNA and mRNA expression profiles
Potential therapies for residual hepatoblastoma following incomplete ablation treatment in a nude mouse subcutaneous xenograft model based on lncRNA and mRNA expression profiles
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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疗法
DOI：
10.3892/or.2020.7545
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发表时间：
2020-06-01
期刊：
影响因子：
4.2
通讯作者：
Yang, Hong
中科院分区：
文献类型：
--
作者：
Wang, Xiao-Dong;Peng, Jin-Bo;Yang, Hong
肝癌射频消融（RFA）治疗后肿瘤复发是影响患者预后的重要因素。此外，RFA后残留肝母细胞瘤（HB）组织中长链非编码RNA（lncRNA）的生物学作用在很大程度上仍然未知。本研究采用基因芯片技术，在裸鼠皮下异种移植模型中，研究了4对HB组织（不完全消融处理和未处理）中lncRNA和mRNA的表达。随后，使用生物信息学分析来了解所鉴定的mRNA的功能和途径。最后，进行连接图（CMap）分析，以确定残留HB组织的潜在治疗策略。与未处理的裸鼠皮下移植瘤模型相比，在实验组中，检测到740个lncRNA和663个mRNA的表达有显著差异。随后的生物信息学分析显示，差异表达的mRNA在与抗原加工、内源性抗原呈递、细胞代谢过程调控、MAPK信号传导和细胞周期调控相关的通路中显著富集。此外，通过CMap分析确定了6种化合物（丙戊酸、二甲双胍、坦司匹霉素、渥曼青霉素、氟维司群和MK-886）作为治疗残留HB组织的潜在治疗药物。这些发现为HB患者RFA治疗后残留HB的发病机制和侵袭性肿瘤复发的潜在治疗策略提供了新的见解。
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.