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微小RNA在神经母细胞瘤化疗耐药形成中的潜在作用

Potential Role of miRNAs in the Acquisition of Chemoresistance in Neuroblastoma.

作者信息

Marengo Barbara, Pulliero Alessandra, Corrias Maria Valeria, Leardi Riccardo, Farinini Emanuele, Fronza Gilberto, Menichini Paola, Monti Paola, Monteleone Lorenzo, Valenti Giulia Elda, Speciale Andrea, Perri Patrizia, Madia Francesca, Izzotti Alberto, Domenicotti Cinzia

机构信息

Department of Experimental Medicine, University of Genova, 16100 Genova, Italy.

Department of Health Sciences, University of Genova, 16100 Genova, Italy.

出版信息

J Pers Med. 2021 Feb 7;11(2):107. doi: 10.3390/jpm11020107.

DOI:10.3390/jpm11020107
PMID:33562297
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7916079/
Abstract

Neuroblastoma (NB) accounts for about 8-10% of pediatric cancers, and the main causes of death are the presence of metastases and the acquisition of chemoresistance. Metastatic NB is characterized by amplification that correlates with changes in the expression of miRNAs, which are small non-coding RNA sequences, playing a crucial role in NB development and chemoresistance. In the present study, miRNA expression was analyzed in two human -amplified NB cell lines, one sensitive (HTLA-230) and one resistant to Etoposide (ER-HTLA), by microarray and RT-qPCR techniques. These analyses showed that miRNA-15a, -16-1, -19b, -218, and -338 were down-regulated in ER-HTLA cells. In order to validate the presence of this down-regulation in vivo, the expression of these miRNAs was analyzed in primary tumors, metastases, and bone marrow of therapy responder and non-responder pediatric patients. Principal component analysis data showed that the expression of miRNA-19b, -218, and -338 influenced metastases, and that the expression levels of all miRNAs analyzed were higher in therapy responders in respect to non-responders. Collectively, these findings suggest that these miRNAs might be involved in the regulation of the drug response, and could be employed for therapeutic purposes.

摘要

神经母细胞瘤（NB）约占儿童癌症的8 - 10%，主要死亡原因是存在转移灶和获得化疗耐药性。转移性NB的特征是基因扩增，这与微小RNA（miRNA）表达的变化相关，miRNA是小的非编码RNA序列，在NB的发展和化疗耐药性中起关键作用。在本研究中，通过微阵列和逆转录定量聚合酶链反应（RT-qPCR）技术，分析了两种人源基因扩增的NB细胞系中的miRNA表达，一种敏感细胞系（HTLA - 230）和一种对依托泊苷耐药的细胞系（ER - HTLA）。这些分析表明，miRNA - 15a、- 16 - 1、- 19b、- 218和- 338在ER - HTLA细胞中表达下调。为了在体内验证这种下调的存在，分析了这些miRNA在治疗有反应和无反应的儿科患者的原发性肿瘤、转移灶和骨髓中的表达。主成分分析数据表明，miRNA - 19b、- 218和- 338的表达影响转移，并且所有分析的miRNA的表达水平在治疗有反应者中高于无反应者。总体而言，这些发现表明这些miRNA可能参与药物反应的调节，并可用于治疗目的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127e/7916079/0a87b8122a08/jpm-11-00107-g007.jpg
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