Identification of Tumor Suppressive miR-144-5p Targets: FAM111B Expression Accelerates the Malignant Phenotypes of Lung Adenocarcinoma

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 <i>miR-144-5p</i> (the passenger strand derived from pre-<i>miR-144</i>) was significantly downregulated in LUAD tissues. The aim of this study was to identify therapeutic target molecules controlled by <i>miR-144-5p</i> in LUAD cells. Ectopic expression assays demonstrated that <i>miR-144-5p</i> 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 <i>miR-144-5p</i> in LUAD cells based on our in silico analysis. We focused on a family with sequence similarity 111 member B (<i>FAM111B</i>) and investigated its cancer-promoting functions in LUAD cells. Luciferase reporter assay showed that expression of <i>FAM111B</i> was directly regulated by <i>miR-144-5p</i> in LUAD cells. <i>FAM111B</i> 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 <i>FAM111B</i>-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.