Alves Letícia Ferreira, Geraldo Murilo Vieira
Department of Structural and Functional Biology, University of Campinas (UNICAMP), São Paulo, Brazil.
Front Oncol. 2023 Jan 26;13:1039654. doi: 10.3389/fonc.2023.1039654. eCollection 2023.
Papillary thyroid carcinoma (PTC) is the most prevalent histotype of thyroid cancer and the presence of BRAFV600E mutation in these tumors is related to the malignancy and prognosis of the disease. In recent years attention has been focused on the role of microRNAs in the biology of PTC cells, especially in their role in the modulation of pathways related to tumorigenesis. DLK1-DIO3-derived miRNAs have been shown to play important roles in tumor context and are globally downregulated in PTC.
Based on a previous in silico target prediction and gene enrichment analysis, we identified miR-495-3p as the candidate with the highest tumor suppressor potential role in PTC among DLK1-DIO3-derived miRNAs. We used bioinformatics and an in vitro model of miR-495-3p overexpression to further understand the influence of this molecule on the tumorigenic processes of PTC.
Overexpression of miR-495-3p impaired cell migration and invasion of PTC cells harboring the BRAFV600E mutation and affected the expression of targets predicted in the bioinformatic analysis, such as TGFB2, EREG and CCND1.
Overall, our results indicate that the loss of miR-495-3p expression during PTC development might play an important role in its progression.
甲状腺乳头状癌（PTC）是甲状腺癌最常见的组织学类型，这些肿瘤中BRAFV600E突变的存在与疾病的恶性程度和预后相关。近年来，人们的注意力集中在微小RNA在PTC细胞生物学中的作用，尤其是它们在调节与肿瘤发生相关途径中的作用。已证明DLK1-DIO3衍生的微小RNA在肿瘤环境中起重要作用，并且在PTC中整体下调。
基于先前的计算机靶标预测和基因富集分析，我们确定miR-495-3p是DLK1-DIO3衍生的微小RNA中在PTC中具有最高肿瘤抑制潜在作用的候选者。我们使用生物信息学和miR-495-3p过表达的体外模型来进一步了解该分子对PTC肿瘤发生过程的影响。
miR-495-3p的过表达损害了携带BRAFV600E突变的PTC细胞的迁移和侵袭，并影响了生物信息学分析中预测的靶标的表达，如TGFB2、EREG和CCND1。
总体而言，我们的结果表明，PTC发展过程中miR-495-3p表达的缺失可能在其进展中起重要作用。
