UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France.
ARNA Laboratory, Institut National de la Santé et de la Recherche Médicale U1212, Université de BordeauxBordeaux, France.
Front Cell Infect Microbiol. 2017 May 16;7:185. doi: 10.3389/fcimb.2017.00185. eCollection 2017.
infection is considered as an excellent model of chronic inflammation-induced tumor development. Our project focuses on gastric MALT lymphoma (GML) related to infection and mediated by the chronic inflammatory process initiated by the infection. Recently, microRNAs (miRNAs) have emerged as a new class of gene regulators, which play key roles in inflammation and carcinogenesis acting as oncogenes or tumor suppressors. Their precise characterization in the development of inflammation and their contribution in regulating host cells responses to infection by have been little explored. Our goal was to analyze the changes in miRNAs in a GML mouse model using BALB/c mice thymectomized at day 3 post-birth (d3Tx model) and to clarify their implication in GML pathogenesis. PCR array followed by RT-qPCR identified five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) overexpressed in the stomachs of GML-developing d3Tx mice infected by . The analysis of their putative targets allowed us to identify TP53INP1, an anti-proliferative and pro-apoptotic protein, as a common target of 4 of the 5 up-regulated miRNAs. We postulate that these miRNAs may act in synergy to promote the development of GML. miR-142a was also overexpressed in mouse sera samples and therefore could serve as a diagnostic marker. hybridization on gastric samples with miR-142a revealed a global up-regulation of this miRNA by the tumor microenvironment at the lymphoma stage. Dysregulation of miR-21a, miR-135b, miR-142a, miR-150, miR-155 could play a critical role in the pathogenesis of GML and might offer potential applications as therapeutic targets and novel biomarkers for this disease.
感染被认为是慢性炎症诱导肿瘤发展的极好模型。我们的项目专注于与感染相关的胃黏膜相关淋巴组织（MALT）淋巴瘤（GML），并由感染引发的慢性炎症过程介导。最近，microRNAs（miRNAs）作为一类新的基因调节剂出现，它们作为癌基因或肿瘤抑制因子在炎症和癌变中发挥关键作用。它们在炎症发展中的精确特征及其在调节宿主细胞对感染的反应中的作用在很大程度上尚未得到探索。我们的目标是使用在出生后第 3 天（d3Tx 模型）进行胸腺切除术的 BALB/c 小鼠分析 GML 小鼠模型中的 miRNAs 变化，并阐明它们在 GML 发病机制中的作用。PCR 阵列随后进行 RT-qPCR 鉴定出在由感染的 GML 发展中的 d3Tx 小鼠的胃中过表达的 5 种 miRNAs（miR-21a、miR-135b、miR-142a、miR-150、miR-155）。对它们的假定靶标的分析使我们能够确定 TP53INP1，一种抗增殖和促凋亡蛋白，是 4 种上调 miRNA 的共同靶标。我们假设这些 miRNA 可能协同作用促进 GML 的发展。miR-142a 也在小鼠血清样本中过表达，因此可以作为诊断标志物。miR-142a 在胃样本上的杂交显示肿瘤微环境在淋巴瘤阶段使该 miRNA 全面上调。miR-21a、miR-135b、miR-142a、miR-150、miR-155 的失调可能在 GML 的发病机制中发挥关键作用，并可能作为该疾病的治疗靶点和新型生物标志物提供潜在应用。
