Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Division of Gastroenterology, Hepatology & Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Cancer Rep (Hoboken). 2023 Jan;6(1):e1685. doi: 10.1002/cnr2.1685. Epub 2022 Jul 20.
Pediatric hepatocellular carcinoma (HCC) is a group of liver cancers whose mechanisms behind their pathogenesis and progression are poorly understood.
We aimed to identify alterations in the expression of miRNAs and their putative target mRNAs in not only tumor tissues of patients with pediatric HCC but also in corresponding non-tumorous background livers by using liver tissues without underlying liver disease as a control.
We performed a small-scale miRNA and mRNA profiling of pediatric HCC (consisting of fibrolamellar carcinoma [FLC] and non-FLC HCC) and paired liver tissues to identify miRNAs whose expression levels differed significantly from control livers without underlying liver disease. ToppMiR was used to prioritize both miRNAs and their putative target mRNAs in a gene-annotation network, and the mRNA profile was used to refine the prioritization. Our analysis generated prioritized lists of miRNAs and mRNAs from the following three sets of analyses: (a) pediatric HCC versus control; (b) FLC versus control; and (c) corresponding non-tumorous background liver tissues from the same patients with pediatric HCC versus control. No liver disease liver tissues were used as the control group for all analyses. Many miRNAs whose expressions were deregulated in pediatric HCC were consistent with their roles in adult HCC and/or other non-hepatic cancers. Our gene ontology analysis of target mRNAs revealed enrichment of biological processes related to the sustenance and propagation of cancer and significant downregulation of metabolic processes.
Our pilot study indicates that alterations in miRNA-mRNA networks were detected in not only tumor tissues but also corresponding non-tumorous liver tissues from patients with pediatric HCC, suggesting multi-faceted roles of miRNAs in disease progression. Our results may lead to novel hypotheses for future large-scale studies.
小儿肝细胞癌（HCC）是一组肝脏癌症，其发病机制和进展背后的机制尚未完全了解。
我们旨在通过使用无潜在肝脏疾病的肝脏组织作为对照，不仅在小儿 HCC 患者的肿瘤组织中，而且在相应的非肿瘤性背景肝脏中，鉴定 miRNA 的表达变化及其潜在的靶 mRNAs。
我们对小儿 HCC（包括纤维板层癌[FLC]和非 FLC HCC）和配对的肝脏组织进行了小规模的 miRNA 和 mRNA 谱分析，以鉴定表达水平与无潜在肝脏疾病的对照肝脏明显不同的 miRNA。ToppMiR 用于在基因注释网络中对 miRNA 和潜在靶 mRNAs 进行优先级排序，mRNA 谱用于细化优先级排序。我们的分析从以下三组分析中生成了 miRNA 和 mRNAs 的优先列表：（a）小儿 HCC 与对照；（b）FLC 与对照；（c）来自同一小儿 HCC 患者的相应非肿瘤性背景肝脏与对照。所有分析均将无肝脏疾病的肝脏组织用作对照组。在小儿 HCC 中表达失调的许多 miRNA 与其在成人 HCC 和/或其他非肝脏癌症中的作用一致。我们对靶 mRNAs 的基因本体分析揭示了与癌症维持和传播相关的生物学过程的富集，以及代谢过程的显著下调。
我们的初步研究表明，不仅在肿瘤组织中，而且在小儿 HCC 患者的相应非肿瘤性肝脏组织中，都检测到 miRNA-mRNA 网络的改变，这表明 miRNA 在疾病进展中具有多方面的作用。我们的结果可能为未来的大规模研究提出新的假设。
