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Lung adenocarcinoma (LUAD) is the most aggressive cancer and the prognosis of these patients is unfavorable. We revealed that the expression levels of both strands of <i>miR-99a</i> (<i>miR-99a-5p</i> and <i>miR-99a-3p</i>) were significantly suppressed in several cancer tissues. Analyses of large The Cancer Genome Atlas (TCGA) datasets showed that reduced <i>miR-99a-5p</i> or <i>miR-99a-3p</i> expression is associated with worse prognoses in LUAD patients (disease-free survival (DFS): <i>p</i> = 0.1264 and 0.0316; overall survival (OS): <i>p</i> = 0.0176 and 0.0756, respectively). Ectopic expression of these miRNAs attenuated LUAD cell proliferation, suggesting their tumor-suppressive roles. Our in silico analysis revealed 23 putative target genes of pre-<i>miR-99a</i> in LUAD cells. Among these targets, high expressions of 19 genes were associated with worse prognoses in LUAD patients (OS: <i>p</i> < 0.05). Notably, <i>FAM64A</i> was regulated by both <i>miR-99a-5p</i> and <i>miR-99a-3p</i> in LUAD cells, and its aberrant expression was significantly associated with poor prognosis in LUAD patients (OS: <i>p</i> = 0.0175; DFS: <i>p</i> = 0.0276). <i>FAM64A</i> knockdown using siRNAs suggested that elevated <i>FAM64A</i> expression contributes to cancer progression. Aberrant FAM64A expression was detected in LUAD tissues by immunostaining. Taken together, our miRNA-based analysis might be effective for identifying prognostic and therapeutic molecules in LUAD.