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

Tumour Biol. 2017 Jun;39(6):1010428317705334. doi: 10.1177/1010428317705334.

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.

Keywords: Curcumin; RNA sequencing; cell migration; extracellular matrix receptors; lung cancer.

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen Type V / biosynthesis*
  • Collagen Type V / genetics
  • Curcumin / administration & dosage*
  • Gene Expression Regulation, Neoplastic / drug effects
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Integrin alpha2 / biosynthesis*
  • Integrin alpha2 / genetics
  • Integrin alpha3 / biosynthesis*
  • Integrin alpha3 / genetics
  • Laminin / biosynthesis*
  • Laminin / genetics
  • Mice
  • RNA, Messenger / biosynthesis
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / genetics
  • Xenograft Model Antitumor Assays

Substances

  • COL5A1 protein, human
  • Collagen Type V
  • ITGA2B protein, human
  • ITGA3 protein, human
  • Integrin alpha2
  • Integrin alpha3
  • Laminin
  • RNA, Messenger
  • Receptors, Cell Surface
  • extracellular matrix receptor
  • laminin alpha5
  • Curcumin