BACKGROUND: A thorough understanding of gastric cancer at the molecular level is urgently needed. One prominent oncogenic microRNA, miR-21, was previously reported to be upregulated in gastric cancer. METHODS: We performed an unbiased search for downstream messenger RNA targets of miR-21, based on miR-21 dysregulation, by using human tissue specimens and the MKN28 human gastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay. RESULTS: This search identified Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3'UTR. miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers, suggesting a regulatory mechanism that included both of these molecules. Furthermore, Serpini1 induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting its potential tumour-suppressive function in the stomach. CONCLUSION: Taken together, these data suggest that in a subgroup of gastric cancers, miR-21 is upregulated, inducing downregulation of Serpini1, which in turn releases the G1-S transition checkpoint, with the end result being increased tumour growth.
BACKGROUND: A thorough understanding of gastric cancer at the molecular level is urgently needed. One prominent oncogenic microRNA, miR-21, was previously reported to be upregulated in gastric cancer. METHODS: We performed an unbiased search for downstream messenger RNA targets of miR-21, based on miR-21 dysregulation, by using human tissue specimens and the MKN28humangastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay. RESULTS: This search identified Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3'UTR. miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers, suggesting a regulatory mechanism that included both of these molecules. Furthermore, Serpini1 induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting its potential tumour-suppressive function in the stomach. CONCLUSION: Taken together, these data suggest that in a subgroup of gastric cancers, miR-21 is upregulated, inducing downregulation of Serpini1, which in turn releases the G1-S transition checkpoint, with the end result being increased tumour growth.
Authors: A S Fleisher; M Esteller; G Tamura; A Rashid; O C Stine; J Yin; T T Zou; J M Abraham; D Kong; S Nishizuka; S P James; K T Wilson; J G Herman; S J Meltzer Journal: Oncogene Date: 2001-01-18 Impact factor: 9.867
Authors: George Adrian Calin; Calin Dan Dumitru; Masayoshi Shimizu; Roberta Bichi; Simona Zupo; Evan Noch; Hansjuerg Aldler; Sashi Rattan; Michael Keating; Kanti Rai; Laura Rassenti; Thomas Kipps; Massimo Negrini; Florencia Bullrich; Carlo M Croce Journal: Proc Natl Acad Sci U S A Date: 2002-11-14 Impact factor: 11.205
Authors: T Tsuchiya; G Tamura; K Sato; Y Endoh; K Sakata; Z Jin; T Motoyama; O Usuba; W Kimura; S Nishizuka; K T Wilson; S P James; J Yin; A S Fleisher; T Zou; S G Silverberg; D Kong; S J Meltzer Journal: Oncogene Date: 2000-07-27 Impact factor: 9.867
Authors: Michael Z Michael; Susan M O' Connor; Nicholas G van Holst Pellekaan; Graeme P Young; Robert J James Journal: Mol Cancer Res Date: 2003-10 Impact factor: 5.852
Authors: Yuriko Mori; Fumiaki Sato; Florin M Selaru; Andreea Olaru; Kellie Perry; Martha C Kimos; Gen Tamura; Nagahide Matsubara; Suna Wang; Yan Xu; Jing Yin; Tong-Tong Zou; Barbara Leggett; Joanne Young; Toshihiro Nukiwa; O Colin Stine; John M Abraham; David Shibata; Stephen J Meltzer Journal: Cancer Res Date: 2002-07-01 Impact factor: 12.701