Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR-92a

Abstract

Lung adenocarcinoma (LUAD) is one of the most prevalent malignancies. However, its mechanism and therapeutic strategy remain to be clarified. Mangiferin is a flavonoid derived from the leaves of mango trees of the lacquer family that has many pharmacological and physiological effects. This research aimed to elucidate the biological effect of mangiferin in LUAD cell lines and clarify the in vitro mechanism of mangiferin. Mangiferin was shown to significantly restrain the proliferation of LUAD cells (A549, H1299, and H2030 cells) in a dose- and time-dependent manner. Furthermore, mangiferin was capable of stimulating apoptosis, and more cells were blocked in G1 and S phase in the mangiferin-treated cells than in those not treated with mangiferin. Microarrays and micro-RNA sequencing data suggested that there is a higher level of miR-27b and miR-92a in LUAD tissues than in non-LUAD tissues. Additional experiments indicated that mangiferin may be related to the downregulated levels of miR-92a and miR-27b. In conclusion, mangiferin likely regulates proliferation and apoptosis in LUAD cells by reducing the expression levels of miR-92a and miR-27b.

Figure 1

The chemical structure depiction of mangiferin (C₁₉H₁₈O₁₁).

Figure 2

Mangiferin suppresses the proliferation of lung adenocarcinoma cells. (a) A549 cells. (b) H1299 cells. (c) H2030 cells.

Figure 3

Cell cycle analysis was performed in A549 (a), H1299 (b), and H2030 (c) cells treated with mangiferin.

Figure 4

Flow cytometry was performed in A549 ((a) 0 μg/ml; (b) 12.5 μg/ml; (c) 100 μg/ml), H1299 ((d) 0 μg/ml; (e) 12.5 μg/ml; (f) 100 μg/ml), and H2030 ((g) 0 μg/ml; (h) 12.5 μg/ml; (i) 100 μg/ml) cells treated with mangiferin.

Figure 5

Expression of miR-27b-5p (a, c) and miR-92a-1-5p (b, d) in lung adenocarcinoma tissues from GEO and TCGA database.

Figure 6

The expression levels of miR-27b-5p and miR-92a-5p in LUAD cells treated by mangiferin (CG: control group; EG: experimental group).

Figure 7

Integration analysis of potential target genes. (a) Gene Ontology analysis; (b) PPI network of genes (number of nodes: 153, number of edges: 239, PPI enrichment P value: <1.0e−16).