A detailed image of rutin underlying intracellular signaling pathways in human SW480 colorectal cancer cells based on miRNAs‐lncRNAs‐mRNAs‐TFs interactions

Abstract

Natural dietary ingredients like flavonoids are important for body improvement against diseases. The flavonol rutin is widely found in fruits and vegetables and shows significant anticancer properties. However, the underlined signaling pathways have not been elucidated yet. In this study, the impacts of various doses of rutin (400–700 mM/ml) have been examined on human colon cancer SW480 cells metabolism, cell cycle, and apoptosis. The transcriptome was analyzed by bioinformatics tools and the interactions between rutin modulated microRNAs (miRNAs), long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and transcription factors (TFs) were built, filtered and enriched. A dose of 600 mM of rutin significantly decreased cells metabolic activity, halved the population and arrested the cell cycle at the sub‐G1 phase. The enrichment analysis of miRNAs‐lncRNAs‐mRNAs‐TFs network showed that these effects were mediated through alteration of glucose, lipid, and protein metabolism, modulating endoplasmic reticulum stress responses, negative regulation of cell cycle process, and inducing the extrinsic and intrinsic apoptotic signaling pathways. Additionally, the key parent nodes of each annotation were illustrated. These findings create a detailed image of rutin underlying intracellular signaling pathways in CRC and also help us to better understand the role of dietary natural compounds in cancer treatment.

Molecular mechanisms of anticancer effect of rutin

“…Metabolic activities of the cells were reducing, the population was halved and the cell cycle was ceased at the sub-G1 phase when rutin was applied. According to the enriching analyses of miRNAs-lncRNAs-mRNAs-TFs network, altering glucose, lipid, and protein metabolism led to mediation of the impacts, while endoplasmic reticulum stress reactions were modulated, the cell cycles processes were negatively regulated, and the internal as well as external apoptotic signaling pathways were induced (Nasri Nasrabadi et al, 2019).…”

High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery

“…The results showed that the cell metabolism activity was significantly reduced, and the cell cycle was inhibited below G1 phase in rutintreated cells. Enrichment analysis of the miRNAs-lncRNAs-mRNAs-TFs network showed that these effects were mediated by changes in glucose, lipid, and protein metabolism, regulation of endoplasmic reticulum stress response, negative regulation of cell cycle processes, and induction of intracellular and extracellular apoptotic signaling pathways (Nasri Nasrabadi et al, 2019). Zhao et al found that Celastrol alleviated cholestatic liver injury in mice through activation of sirtuin 1 (SIRT1), increasing the farnesoid X receptor (FXR) signaling pathway, and inhibiting the nuclear factorkappa B (NF-kB) and P53 signaling pathways by RNA-seq technology (Zhao et al, 2019).…”

Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach

“…Rutin ameliorates the metabolism of colon cancer SW480 cells, increases apoptosis, and arrests the cell cycle at the sub-G1 phase. Analysis of microRNAs, long noncoding RNAs, messenger RNAs, and transcription factors revealed that these promising effects were associated with the modulation of dysregulated intracellular signaling pathways involved in glucose, lipid, and protein metabolism, extrinsic and intrinsic apoptosis, reticulum stress responses, and cell cycle stages [ 120 ]. Future studies should investigate the proposed panel in other cancer models.…”