MiRNA-625-3p as novel biomarker promotes cell proliferation and metastasis of lung adenocarcinoma by targeting KLF9

Abstract Background. MicroRNAs (miRNAs) are emerging as potential blood-based biomarkers and involved carcinogenesis for various cancers, including lung adenocarcinoma (LUAD). Methods. In the present study, microarray was used to screen 2,549 miRNAs in serum samples (7 LUAD and 7 healthy samples). qRT-PCR was used to validate the expression of miRNA in serum samples from 30 LUAD and 30 normal individuals. Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of miR-625-3p. Cell counting kit-8 assay (CCK-8) and Transwell assays were used to explore cell proliferation, migration and invasion. Bioinformatics prediction was applied in the search for the target genes of miR-625-3p. qRT-PCR, western blot and dual luciferase assay were used to validate the target gene of miR-625-3p. A xenograft tumor model was established to evaluate cell proliferation in vivo . Results. MiR-625-3p was the most increased miRNA expressed in LUAD serum samples according to microarray analysis, which was verified in an independent serum sample, as well as in tissues based on TCGA database. And serum miR-625-3p provided a high diagnostic accuracy of LUAD (AUC=0.790, 95%CI:0.6640-0.9152). Functionally, miR-625-3p promoted LUAD cell proliferation, migration and invasion both in vivo and in vitro . Mechanistically, we identified KLF9 as an essential direct target of miR-625-3p, miR-625-3p promoted cell proliferation and metastasis of LUAD by targeting KLF9. Conclusions. Our study identified that miR-625-3p plays an oncogenic role in LUAD, which promoted proliferation and migration through targeting KLF9. MiR-625-3p might be a potential novel diagnostic biomarker and target for LUAD therapy.