Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Int J Mol Sci. 2024 Sep 16;25(18):9974. doi: 10.3390/ijms25189974.
Accumulating evidence suggests that the passenger strands microRNAs (miRNAs) derived from pre-miRNAs are closely involved in cancer pathogenesis. Analysis of our miRNA expression signature of lung adenocarcinoma (LUAD) and The Cancer Genome Atlas (TCGA) data revealed that (the passenger strand derived from pre-) was significantly downregulated in LUAD tissues. The aim of this study was to identify therapeutic target molecules controlled by in LUAD cells. Ectopic expression assays demonstrated that attenuated LUAD cell aggressiveness, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. A total of 18 genes were identified as putative cancer-promoting genes controlled by in LUAD cells based on our in silico analysis. We focused on a family with sequence similarity 111 member B () and investigated its cancer-promoting functions in LUAD cells. Luciferase reporter assay showed that expression of was directly regulated by in LUAD cells. knockdown assays showed that LUAD cells significantly suppressed malignant phenotypes, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. Furthermore, we investigated the -mediated molecular networks in LUAD cells. Identifying target genes regulated by passenger strands of miRNAs may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.
越来越多的证据表明,源自前体 miRNA 的过客 miRNA 与癌症的发病机制密切相关。分析我们肺腺癌 (LUAD) 的 miRNA 表达特征和癌症基因组图谱 (TCGA) 数据显示,(源自前体的过客链)在 LUAD 组织中显著下调。本研究旨在鉴定由 调控的 LUAD 细胞中的治疗靶分子。异位表达实验表明, 减弱了 LUAD 细胞的侵袭能力,如抑制细胞增殖、迁移和侵袭能力,并诱导细胞周期停滞和凋亡细胞。基于我们的计算机分析,共有 18 个基因被确定为受 调控的潜在致癌基因。我们专注于具有序列相似性 111 成员 B ()的家族,并研究了其在 LUAD 细胞中的致癌功能。荧光素酶报告基因检测显示, 在 LUAD 细胞中的表达受 直接调控。 敲低实验表明,LUAD 细胞显著抑制恶性表型,如抑制细胞增殖、迁移和侵袭能力,并诱导细胞周期停滞和凋亡细胞。此外,我们还研究了 -介导的 LUAD 细胞中的分子网络。确定由 miRNA 过客链调控的靶基因可能有助于发现 LUAD 的诊断标志物和治疗靶点。