Analysis of change in microRNA expression profiles of lung cancer A549 cells treated with Radix tetrastigma hemsleyani flavonoids

Abstract

BackgroundThe aim of this study was to determine the inhibition effects of Radix tetrastigma hemsleyani (RTH) flavonoids on human lung adenocarcinoma A549 cells and the underlying molecular mechanism. RTH is an important Chinese traditional herb that has been widely used in cancer therapy. As an important type of active substance, RTH flavones (RTHF) have been shown to have good antiproliferative effects on various cancer cells. MicroRNAs (miRNAs) are small, noncoding RNA molecules that play important roles in cancer progression and prevention. However, the miRNA profile of RTHF-treated A549 cells has not yet been studied.Materials and methodsThe miRNA expression profile changes of A549 cell treated with RTHF were determined using the miRNA-seq analysis. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed miRNAs′ (DE-miRNAs) target genes were carried out.ResultsIn this study, we identified 162 miRNAs that displayed expression changes >1.2-fold in RTHF-treated A549 cells. GO analysis results showed that target genes of DE-miRNAs were significantly enriched in protein binding, binding, cell, cell part, intracellular, cellular process, single-organism process, and single-organism cellular process. Pathway analysis illustrated that target genes of DE-miRNAs are mainly involved in endocytosis, axon guidance, lysosome, melanogenesis, and acute myeloid leukemia pathway.ConclusionThese results may assist in the better understanding of the anticancer effects of RTHF in A549 cells.

<p>Bioinformatic analysis of miR-4792 regulates <em>Radix Tetrastigma hemsleyani</em> flavone to inhibit proliferation, invasion, and induce apoptosis of A549 cells</p>

“…There was a significant decrease in cell proliferation in the miR-4792 mimics and RTHF + miRNA NC groups compared to the control group (miRNA NC group), indicating that RTHF inhibited A549 cell proliferation by upregulating the expression of miR-4792, and the inhibition effect was similar to that of miR-4792 mimics. Compared to the RTHF + miRNA NC group in which only RTHF played a role in cell proliferation inhibition, cell proliferation in the RTHF + miR-4792 inhibitor group was significantly increased, suggesting that miR-4792 played a more important role than other DE-miRNAs found in our previous studies in the cell proliferation inhibition by RTHF 13. The cell viability assays revealed that miR-4792 had effects on inhibiting cell proliferation, and suggested it might have played an important regulatory role in RTHF-mediated inhibition of A549 cell proliferation.…”

“…The purified extract was freeze-dried to RTHF power and then dissolved in Roswell Park Memorial Institute 1640 culture medium to 10 mg/mL and finally filtered through a 0.45 µm filter for use. In our previous experiments, through chemical composition analysis by HPLC–mass spectrometry (MS) and HPLC–MS/MS, we found that RTHF used in this study mainly included six foregone active substances, including kaempferol (PubChem CID: 5280823, 12.57%), kaempferol-3- O -neohesperidoside (PubChem CID: 44575467, 19.11%), malvidin-3-glucoside (PubChem CID: 443652, 10.23%), myricitrin (PubChem CID: 5281673, 8.56%), baohuoside (PubChem CID: 5488822, 9.98%), and isoschaftoside (PubChem CID: 3084995, 13.28%) 13…”

“…Depending upon the nature of their target gene(s), miRNAs may function as tumor suppressors or oncogenes by downregulating target mRNAs. In our previous studies, expression changes of miRNAs in RTHF-treated A549 cells were analyzed using miRNA-seq techniques, and 162 miRNAs were found to be differentially expressed after RTHF treatment 13. Among the differentially expressed miR-NAs (DE-miRNAs), miR-4792 was found to be upregulated 6.65-fold, and previous studies have found its participation in numerous biological processes of many cancers by targeting a broad set of cell factors 13.…”

“…In our previous studies, expression changes of miRNAs in RTHF-treated A549 cells were analyzed using miRNA-seq techniques, and 162 miRNAs were found to be differentially expressed after RTHF treatment 13. Among the differentially expressed miR-NAs (DE-miRNAs), miR-4792 was found to be upregulated 6.65-fold, and previous studies have found its participation in numerous biological processes of many cancers by targeting a broad set of cell factors 13. Therefore, miR-4792 has the potential to become one of the important potential therapeutic agents for lung cancer by many drugs such as RTHF.…”

The Phytochemistry, Pharmacology, and Quality Control of Tetrastigma hemsleyanum Diels & Gilg in China: A Review

“…In addition, the study has found that the content of total flavonoids in leaves of TDG ranges from 13.38 to 28.67 mg· g -1 ( Fan et al., 2017 ). More than 30 flavonoids isolated and identified from TDG, including kaempferol-7-O-α-L-rhamnopyranosyl-3-O-β-D-glucopyranoside (1), apigenin-6-C-α-L-arabinopyranosyl-(1-4)-α-L-rhamnopyranoside (2), and apigenin-8-C-α-L-arabinopyranosyl-(1-4)-α-L-rhamnopyranoside (3), apigenin-6, 8-di-C-β-D-glucopyranoside (4), kaempferol (5), quercetin (6), kaempferol 3-neohesperidoside (7), rhamnocitrin (8), kaempferol-7-O-α-L-rhamnopyranoside (9), aromadendrin (10), kaempferol-3-O-β-D-glucopyranoside (11), isoquercetin (12), nicotifiorin (kaempferol-3-o-rutoside, 13), robinin (14), rutin (15), astragaloside (16), catechin (17), L-epicatechin (18), epigallocatechin (19), procyanidin B2 (20), procyanidin B1 (21), apigenin (22), quercitrin (23), kaempferitrin (24), apigenin-6-C-β-D-glucopyranoside (Isovitexin, 25), apigenin-8-C-α-L-rhamnopyranosyl-(1-2)-β-D-glucopyranoside (Vitexin-2-O-rhamnoside, 26), apigenin-8-C-β-D-glucopyranoside (Vitexin, 27), apigenin-8-C-β-D-glucopyranoside-(1-4)-β-D-glucopyranoside (Vitexin-4’’-O-glucoside, 28), orientin (29), isoorientin (30), malvidin-3-glucoside (31), myricitrin (32), baohuosid I (33), and isoschaftoside (34) ( Liu, 2000 ; Liu et al., 2002 ; Li et al., 2003 ; Guo, 2013 ; Zeng, 2013 ; Fan et al., 2014 ; Fu et al., 2015 ; Lin et al., 2015 ; Liu et al., 2018 ). The structure of some flavonoids is shown in Figure 2 , with the names of all constituents being listed in Table 1 .…”