Capuano Cecilia, Moccia Valentina, Molinari Antonella, Torrigiani Filippo, Ferro Livia, Ferraresso Serena, Bonsembiante Federico, Leo Chiara, Zappulli Valentina
Anicura Istituto Veterinario di Novara, Granozzo Monticello, Italy.
Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Italy.
Front Vet Sci. 2024 Aug 29;11:1461506. doi: 10.3389/fvets.2024.1461506. eCollection 2024.
Canine lymphoma (cL) is one of the most frequent cancers in dogs. The T-cell lymphoma (TcL) is not the most common phenotype but presents an aggressive behavior. MicroRNAs (miRNAs), are small, single-stranded, non-coding RNA molecules which can circulate freely in blood or be associated with extracellular vesicles (EVs). The dysregulation of certain miRNAs has been identified in numerous types of human cancers and they have been largely investigated as possible tumors biomarkers in human medicine, while research in veterinary oncology is still scarce. The aim of this study was to compare the expression patterns of free circulating and EV-associated miRNAs in dogs with T-cell lymhoma (TcL) and healthy dogs.
Eight dogs with TcL were selected as the lymphoma group (LG) and eight dogs were included as controls (Ctrl). Plasma samples were collected at the time of the diagnosis and EVs isolated with ultracentrifugation. miRNAs were extracted from both the circulating EVs and the plasma supernatant, obtaining EV-associated and free-miRNAs. Quantitative real-time PCR was performed to analyze the expression of 88 target miRNAs.
Ten and seven differentially expressed miRNAs between LG and Ctrl were detected in EV-associated and free-miRNAs, respectively. Among EV-associated and free-miRNAs, only has-miR-222-3p was overexpressed in both conditions.
All the differentially expressed miRNAs detected in this study, have been already described as dysregulated in other human or canine cancers. The EV-associated miRNAs, which appear to be more stable and better conserved than free-miRNAs, could be investigated in further larger studies to better assess their use as possible biomarkers for TcL.
犬淋巴瘤（cL）是犬类最常见的癌症之一。T细胞淋巴瘤（TcL）并非最常见的表型，但具有侵袭性。微小RNA（miRNA）是小的单链非编码RNA分子，可在血液中自由循环或与细胞外囊泡（EV）相关联。在多种人类癌症中已发现某些miRNA的失调，并且它们在人类医学中作为可能的肿瘤生物标志物已得到大量研究，而兽医肿瘤学方面的研究仍然很少。本研究的目的是比较患有T细胞淋巴瘤（TcL）的犬和健康犬中游离循环miRNA和与EV相关的miRNA的表达模式。
选择8只患有TcL的犬作为淋巴瘤组（LG），并纳入8只犬作为对照（Ctrl）。在诊断时采集血浆样本，并用超速离心法分离EV。从循环EV和血浆上清液中提取miRNA，得到与EV相关的miRNA和游离miRNA。进行定量实时PCR分析88种靶miRNA的表达。
在与EV相关的miRNA和游离miRNA中，分别检测到LG和Ctrl之间有10种和7种差异表达的miRNA。在与EV相关的miRNA和游离miRNA中，只有has-miR-222-3p在两种情况下均过表达。
本研究中检测到的所有差异表达的miRNA，在其他人类或犬类癌症中均已被描述为失调。与游离miRNA相比，似乎更稳定且保守性更好的与EV相关的miRNA，可在进一步的更大规模研究中进行研究，以更好地评估它们作为TcL可能的生物标志物的用途。
