Open AccessMiR‐133b inhibits growth of human gastric cancer cells by silencing pyruvate kinase muscle‐splicer polypyrimidine tract‐binding protein 1
Author(s) -
Sugiyama Taro,
Taniguchi Kohei,
Matsuhashi Nobuhisa,
Tajirika Toshihiro,
Futamura Manabu,
Takai Tomoaki,
Akao Yukihiro,
Yoshida Kazuhiro
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13091
Subject(s) - pyruvate kinase , pkm2 , polypyrimidine tract binding protein , cancer cell , glycolysis , warburg effect , chemistry , autophagy , microbiology and biotechnology , kinase , cell growth , protein kinase a , cancer research , cancer , biology , apoptosis , biochemistry , messenger rna , metabolism , rna binding protein , genetics , gene
The metabolism in tumor cells shifts from oxidative phosphorylation to glycolysis even in an aerobic environment. This phenomenon is known as the Warburg effect. This effect is regulated mainly by polypyrimidine tract‐binding protein 1 ( PTBP 1 ), which is a splicer of the m RNA for the rate‐limiting enzymes of glycolysis, pyruvate kinase muscle 1 and 2 ( PKM 1 and PKM 2). In the present study, we demonstrated that miR‐133b reduced PTBP 1 expression at translational level and that the expression levels of miR‐133b were significantly downregulated in gastric cancer clinical samples and human cell lines, whereas the protein expression level of PTBP 1 was upregulated in 80% of the 20 clinical samples of gastric cancer examined. Ectopic expression of miR‐133b and knockdown of PTBP 1 in gastric cancer cells inhibited cell proliferation through the induction of autophagy by the switching of PKM isoform expression from PKM 2‐dominant to PKM 1‐dominant. The growth inhibition was partially canceled by an autophagy inhibitor 3‐ MA or a reactive oxygen species scavenger N ‐acetylcysteine. These findings indicated that miR‐133b acted as a tumor‐suppressor through negative regulation of the Warburg effect in gastric cancer cells.