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Knockdown Glucose‐6‐Phosphate Dehydrogenase promotes EMT through downregulation of E‐cadherin by miR‐200b inhibition in A549 cells
Author(s) -
Wu YiHsuan,
Lee YingHsuan,
Chiu Daniel TsunYee
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.50.5
Subject(s) - gene knockdown , epithelial–mesenchymal transition , carcinogenesis , downregulation and upregulation , pentose phosphate pathway , cancer research , ectopic expression , cadherin , chemistry , glucose 6 phosphate dehydrogenase , microrna , microbiology and biotechnology , apoptosis , biology , glycolysis , cell , dehydrogenase , enzyme , biochemistry , gene
Glucose‐6‐phosphate dehydrogenase (G6PD) is a house keeping enzyme and is a rate limiting enzyme in the pentose phosphate shunt to regenerate NADPH. Tumorigenesis is often accompanied by increased glycolysis and G6PD activity. However, treatment with TGF‐β, commonly used to induce epithelial‐mesenchymal transition (EMT), inhibits G6PD expression in tumor cells (Accession No. GDS3710). Therefore, the roles of G6PD on tumorigenesis, particularly on EMT need to be clearly defined. In the present study, whether G6PD modulate EMT process in cancer cells through miRNA was evaluated. G6PD‐knockdown cells showed a more mesenchymal‐like morphology. The changes in morphology were accompanied by increase of migration of these cells. Suppression of epithelial markers, E‐cadherin, and increase of N‐cadherin were observed in G6PD‐knockdown cells. The anticancer miRNAs, especially miR‐200b, a regulator of E‐cadherin expression, was downregulated in G6PD‐knockdown cells as documented by miRNA profiling. Ectopic expression of G6PD in G6PD‐knockdown cells upregulates the expression of miR‐200b and E‐cadherin. Taken together, these results suggest that G6PD plays an important role in downregulating EMT via modulation of miR‐200b in lung epithelial cells. Support or Funding Information Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Tao‐yuan, Taiwan Department of Laboratory Medicine, Chang Gung Memorial Hospital, Lin‐Kou, Taiwan