Our recent research has revealed that passenger strands of certain microRNAs (miRNAs) function as tumor-suppressive miRNAs in cancer cells, e.g., miR-101-5p, miR-143-5p, miR-144-5p, miR-145-3p, and miR-150-3p. Thus, they are important in cancer pathogenesis. Analysis of the miRNA expression signature of breast cancer (BrCa) showed that the expression levels of two miRNAs derived from pre-miR-99a (miR-99a-5p and miR-99a-3p) were suppressed in cancerous tissues. The aim of this study was to identify oncogenic genes controlled by pre-miR-99a that are closely involved in the molecular pathogenesis of BrCa. A total of 113 genes were identified as targets of pre-miR-99a regulation (19 genes modulated by miR-99a-5p, and 95 genes regulated by miR-99a-3p) in BrCa cells. Notably, FAM64A was targeted by both of the miRNAs. Among these targets, high expression of 16 genes (C5orf22, YOD1, SLBP, F11R, C12orf49, SRPK1, ZNF250, ZNF695, CDK1, DNMT3B, TRIM25, MCM4, CDKN3, PRPS, FAM64A, and DESI2) significantly predicted reduced survival of BrCa patients based upon The Cancer Genome Atlas (TCGA) database. In this study, we focused on FAM64A and investigated the relationship between FAM64A expression and molecular pathogenesis of BrCa subtypes. The upregulation of FAM64A was confirmed in BrCa clinical specimens. Importantly, the expression of FAM64A significantly differed between patients with Luminal-A and Luminal-B subtypes. Our data strongly suggest that the aberrant expression of FAM64A is involved in the malignant transformation of BrCa. Our miRNA-based approaches (identification of tumor-suppressive miRNAs and their controlled targets) will provide novel information regarding the molecular pathogenesis of BrCa.

我们最近的研究表明，某些微小 RNA (miRNA) 的过客链在癌细胞中起到抑制肿瘤的 miRNA 的作用，例如miR-101-5p、miR-143-5p、miR-144-5p、miR-145-3p、和miR-150-3p。因此，它们在癌症发病机制中很重要。对乳腺癌 (BrCa) miRNA 表达特征的分析表明，源自 pre - miR-99a的两种 miRNA （miR-99a-5p和miR-99a-3p）在癌组织中的表达水平受到抑制。本研究的目的是鉴定由 pre -miR-99a控制的致癌基因。与 BrCa 的分子发病机制密切相关。总共有 113 个基因被鉴定为BrCa 细胞中 pre - miR-99a调节的靶标（19 个基因受miR-99a-5p调节，95 个基因受miR-99a-3p调节）。值得注意的是，FAM64A被这两种 miRNA 靶向。在这些目标中，16个基因（高表达C5orf22，YOD1，SLBP，F11R，C12orf49，SRPK1，ZNF250，ZNF695，CDK1，DNMT3B，TRIM25，MCM4，基于癌症基因组图谱 (TCGA) 数据库，CDKN3、PRPS、FAM64A和DESI2 ) 显着预测了 BrCa 患者的存活率降低。在这项研究中，我们专注于FAM64A并研究了FAM64A表达与 BrCa 亚型分子发病机制之间的关系。FAM64A的上调在 BrCa 临床标本中得到证实。重要的是，FAM64A的表达在 Luminal-A 和 Luminal-B 亚型患者之间存在显着差异。我们的数据强烈表明FAM64A的异常表达参与 BrCa 的恶性转化。我们基于 miRNA 的方法（识别肿瘤抑制 miRNA 及其控制靶标）将提供有关 BrCa 分子发病机制的新信息。