文章：

肿瘤抑制性miR-30c-1-3p与miR-30c-2-3p调控的致癌靶点：TRIP13促进乳腺癌细胞侵袭性

Oncogenic Targets Regulated by Tumor-SuppressivemiR-30c-1-3pandmiR-30c-2-3p:TRIP13Facilitates Cancer Cell Aggressiveness in Breast Cancer

原文发布日期：21 August 2023

DOI: 10.3390/cancers15164189

类型: Article

开放获取: 是

英文摘要：

Accumulating evidence suggests that themiR-30family act as critical players (tumor-suppressor or oncogenic) in a wide range of human cancers. Analysis of microRNA (miRNA) expression signatures and The Cancer Genome Atlas (TCGA) database revealed that that two passenger strand miRNAs,miR-30c-1-3pandmiR-30c-2-3p, were downregulated in cancer tissues, and their low expression was closely associated with worse prognosis in patients with BrCa. Functional assays showed thatmiR-30c-1-3pandmiR-30c-2-3poverexpression significantly inhibited cancer cell aggressiveness, suggesting these two miRNAs acted as tumor-suppressors in BrCa cells. Notably, involvement of passenger strands of miRNAs is a new concept of cancer research. Further analyses showed that seven genes (TRIP13,CCNB1,RAD51,PSPH,CENPN,KPNA2, andMXRA5) were putative targets ofmiR-30c-1-3pandmiR-30c-2-3pin BrCa cells. Expression of seven genes were upregulated in BrCa tissues and predicted a worse prognosis of the patients. Among these genes, we focused onTRIP13and investigated the functional significance of this gene in BrCa cells. Luciferase reporter assays showed thatTRIP13was directly regulated by these two miRNAs.TRIP13knockdown using siRNA attenuated BrCa cell aggressiveness. Inactivation of TRIP13 using a specific inhibitor prevented the malignant transformation of BrCa cells. Exploring the molecular networks controlled by miRNAs, including passenger strands, will facilitate the identification of diagnostic markers and therapeutic target molecules in BrCa.

摘要翻译： 

越来越多的证据表明，miR-30家族在多种人类癌症中扮演着关键角色（作为肿瘤抑制因子或致癌因子）。通过对微小RNA（miRNA）表达谱及癌症基因组图谱（TCGA）数据库的分析发现，两条过客链miRNA——miR-30c-1-3p和miR-30c-2-3p——在癌组织中表达下调，其低表达与乳腺癌患者的不良预后密切相关。功能实验表明，过表达miR-30c-1-3p和miR-30c-2-3p能显著抑制癌细胞的侵袭能力，提示这两种miRNA在乳腺癌细胞中发挥肿瘤抑制作用。值得注意的是，miRNA过客链的参与是癌症研究的新概念。进一步分析显示，七个基因（TRIP13、CCNB1、RAD51、PSPH、CENPN、KPNA2和MXRA5）可能是miR-30c-1-3p和miR-30c-2-3p在乳腺癌细胞中的潜在靶标。这七个基因在乳腺癌组织中表达上调，并预示患者预后不良。在这些基因中，我们聚焦于TRIP13，研究了该基因在乳腺癌细胞中的功能意义。荧光素酶报告基因实验证实TRIP13直接受这两种miRNA调控。使用siRNA敲低TRIP13可减弱乳腺癌细胞的侵袭性。使用特异性抑制剂使TRIP13失活可阻止乳腺癌细胞的恶性转化。探索由miRNA（包括过客链）调控的分子网络，将有助于识别乳腺癌的诊断标志物和治疗靶点分子。

原文链接：

Oncogenic Targets Regulated by Tumor-SuppressivemiR-30c-1-3pandmiR-30c-2-3p:TRIP13Facilitates Cancer Cell Aggressiveness in Breast Cancer