| Summary: | Based on our miRNA expression signatures, we focused on <i>miR-150-5p</i> (the guide strand) and <i>miR-150-3p</i> (the passenger strand) to investigate their functional significance in lung adenocarcinoma (LUAD). Downregulation of <i>miR-150</i> duplex was confirmed in LUAD clinical specimens. In vitro assays revealed that ectopic expression of <i>miR-150-5p</i> and <i>miR-150-3p</i> inhibited cancer cell malignancy. We performed genome-wide gene expression analyses and in silico database searches to identify their oncogenic targets in LUAD cells. A total of 41 and 26 genes were identified as <i>miR-150-5p</i> and <i>miR-150-3p</i> targets, respectively, and they were closely involved in LUAD pathogenesis. Among the targets, we investigated the oncogenic roles of tensin 4 (<i>TNS4</i>) because high expression of <i>TNS4</i> was strongly related to poorer prognosis of LUAD patients (disease-free survival: <i>p</i> = 0.0213 and overall survival: <i>p</i> = 0.0003). Expression of <i>TNS4</i> was directly regulated by <i>miR-150-3p</i> in LUAD cells. Aberrant expression of TNS4 was detected in LUAD clinical specimens and its aberrant expression increased the aggressiveness of LUAD cells. Furthermore, we identified genes downstream from <i>TNS4</i> that were associated with critical regulators of genomic stability. Our approach (discovery of anti-tumor miRNAs and their target RNAs for LUAD) will contribute to the elucidation of molecular networks involved in the malignant transformation of LUAD.
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