Novel Biomarker miRNA-625-3p Promotes Cell Proliferation and Metastasis of Lung Adenocarcinoma by Targeting KLF9

Abstract

Background: MicroRNAs (miRNAs) are emerging as potential blood-based biomarkers involved in various types of carcinogenesis, including lung adenocarcinoma (LUAD).

Materials and methods: In the present study, microarray was used to screen 2,549 miRNAs in serum samples from seven patients with LUAD and seven from healthy controls. Quantitative real-time polymerase chain reaction was used to validate the expression of miRNA in serum samples from 30 patients with LUAD and 30 heathy individuals. The area under the receiver operating characteristic curve was determined to evaluate the diagnostic capability of miR-625-3p. Cell counting kit-8 assay 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. Quantitative real-time polymerase chain reaction, western blot and dual luciferase assay were used to validate target genes of miR-625-3p. A xenograft tumor model was established to evaluate cell proliferation in vivo.

Results: miR-625-3p was the miRNA most highly expressed in serum samples from patients with LUAD according to microarray analysis, this finding was verified in sera from an independent cohort, as well as in tissues based on The Cancer Genome Atlas database. Serum miR-625-3p provided a high diagnostic accuracy for LUAD (area under the curve=0.790, 95% confidence interval=0.6640-0.9152). Functionally, miR-625-3p promoted LUAD cell proliferation, migration and invasion both in vivo and in vitro. Mechanistically, we found miR-625-3p promoted cell proliferation and metastasis of LUAD by directly targeting KLF transcription factor 9 (Kruppel-like factor 9, KLF9).

Conclusion: Our study identified that miR-625-3p plays an oncogenic role in LUAD, targeting KLF9. miR-625-3p might be a potential novel diagnostic biomarker and target for LUAD therapy.

Keywords: KLF9; LUAD; growth; invasion; miR-625-3p; migration.