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基于长链非编码 RNA 和信使 RNA 表达谱的裸鼠皮下异种移植模型中不完全消融治疗后残余肝母细胞瘤的潜在治疗方法。

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

机构信息

Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

出版信息

Oncol Rep. 2020 Jun;43(6):1915-1927. doi: 10.3892/or.2020.7545. Epub 2020 Mar 16.

DOI:10.3892/or.2020.7545
PMID:32186781
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7160554/
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.

摘要

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 后残余肝母细胞瘤(HB)组织中长链非编码 RNA(lncRNA)的生物学作用在很大程度上尚不清楚。本研究采用基因芯片技术,对裸鼠皮下异种移植模型中 4 对 HB 组织(不完全消融治疗和未治疗)的 lncRNA 和 mRNA 表达进行了检测。随后,通过生物信息学分析来了解鉴定出的 mRNAs 的功能和途径。最后,进行了连接图谱(CMap)分析,以确定残余 HB 组织的潜在治疗策略。与未治疗的裸鼠皮下异种移植模型相比,在实验组中,检测到 740 个 lncRNA 和 663 个 mRNA 的表达存在显著差异。随后,生物信息学分析表明,差异表达的 mRNAs 显著富集于与抗原加工、内源性抗原呈递、细胞代谢过程调控、MAPK 信号转导和细胞周期调控相关的途径中。此外,通过 CMap 分析,还鉴定出了 6 种化合物(丙戊酸、二甲双胍、坦西普酶、渥曼青霉素、氟维司群和 MK-886)可能是治疗 RFA 治疗后 HB 残余组织的潜在治疗药物。这些发现为残余 HB 的发病机制提供了新的见解,并为 HB 患者 RFA 治疗后侵袭性肿瘤复发提供了潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850c/7160554/d0dcea11cdef/OR-43-06-1915-g10.jpg
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