Comprehensive analysis of hsa-miR-654-5p's tumor-suppressing functions

The pivotal roles of miRNAs in carcinogenesis, metastasis, and prognosis have been demonstrated recently in various cancers. This study intended to investigate the specific roles of hsa-miR-654-5p in lung cancer, which was poorly discussed. A series of closed-loop bioinformatic functional analyses were integrated with in vitro experimental validation to explore the overall biological functions and pan-cancer regulation pattern of miR-654-5p. We found that miR-654-5p abundance was significantly elevated in LUAD tissues and correlated with patients survival. 275 potential targets of miR-654-5p were then identified and the miR-654-5p-RNF8 regulation axis was validated in vitro as a proof of concept. Furthermore, we revealed the tumor-suppressing roles of miR-654-5p and demonstrated that miR-654-5p inhibited lung cancer cell epithelial-mesenchymal transition (EMT) process, cell proliferation, and migration using target-based, abundance-based and ssGSEA-based bioinformatic methods and in vitro validation. Following the construction of a protein-protein interaction network, 11 highly interconnected hub genes were identified and a five genes risk scoring model was developed to assess their potential prognostic ability. Our study will not only provide a basic miRNA-mRNA-phenotypes reference map for understanding the function of miR-654-5p in different cancers but also reveal the tumor-suppressing roles and prognostic values of miR-654-5p in lung cancer. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/423719v2_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@15da4caorg.highwire.dtl.DTLVardef@edfbb6org.highwire.dtl.DTLVardef@289028org.highwire.dtl.DTLVardef@1105a2e_HPS_FORMAT_FIGEXP M_FIG C_FIG