Identification of curcumin-inhibited extracellular matrix receptors in non–small cell lung cancer A549 cells by RNA sequencing

Abstract

Curcumin is a potent anti-cancer drug in several types of human cancers. Despite of several preclinical and clinical studies of curcumin, the precise mechanism of curcumin in cancer prevention has remained unclear. In our study, we for the first time investigated whole transcriptome alteration in A549 non-small cell lung cancer (NSCLC) cell lines after treatment with curcumin using RNA sequencing. We found that lots of genes and signaling pathways were significantly altered after curcumin treatment in A549 cells. With bioinformatics approaches (gene ontology, Kyoto Encyclopedia of Genes and Genomes, and STRING), we found that those curcumin altered genes were not only the genes that induce cell death but also those extracellular matrix receptors and mitogen-activated protein kinase signaling pathway genes which regulate cell migration and proliferation. Among those significantly altered genes, eight genes (COL1A1, COL4A1, COL5A1, LAMA5, ITGA3, ITGA2B, DDIT3, and DUSP1) were further examined by quantitative reverse transcription polymerase chain reaction and western blot analysis in four non-small cell lung cancer cell lines. Both in cell lines and in mouse model, the extracellular matrix receptors including the integrin (ITGA3 and ITGA2B), collagen (COL5A1), and laminin (LAMA5) were significantly inhibited by curcumin at messenger RNA and protein levels. Functional studies confirmed that curcumin not only induced A549 cell death but also repressed cell proliferation and migration by regulating extracellular matrix receptors. Collectively, our study suggests that curcumin may be used as a promising drug candidate for intervening lung cancer in future studies.

Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq

“…They may be involved in important biological processes or signaling pathways in tumors, according to the DEG-GO-KEGG pathway network and literatures (Figure 2F). They are BSG26, DERA27, ITGA2B28, SELP29, TGFB1I130, TIMP131, TLN132, and TPM133. We also randomly selected two genes without significant regulation, CD63 and IFITM3 as negative controls.…”

Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells

“…Its elevated expression correlated with cancer metastasis through its interaction with extracellular matrix proteins [ 87 , 158 , 159 , 160 , 161 , 162 ]. Curcumin was reported to downregulate ITGA3 in lung cancer cells and cause inhibition of cell proliferation and invasion and induction of apoptosis [ 163 ]. Therefore, downregulation of ITGA3 by MS13 may inhibit cell proliferation and invasion and induce apoptosis in NCI-H23 cells.…”

Evidence-Based Management of Uterine Fibroids With Botanical Drugs-A Review

“…The ability of curcumin to down-regulate the expression of fibronectin, one of the ECM proteins, which is overexpressed in leiomyoma as compared to normal myometrium, has also been documented ( Malik et al, 2009 ). The significant inhibitory effect of curcumin on the expression of ECM receptors in non-small-cell lung cancer ( Li et al, 2017 ) and reducing the activity of MMP-2 and up-regulating TIMP activity in various cancer cells ( Mitra et al, 2006 ; Hassan and Daghestani, 2012 ; Supriono et al, 2018 ) suggest the possible mechanism of curcumin in producing anti-uterine fibroid activity via reducing the ECM production, thus further study investigating the effects of curcumin on various ECM-related receptors and proteins in leiomyoma cells may be conducted.…”