TY - JOUR
T1 - MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer
AU - Yamanaka, Sumitaka
AU - Olaru, Alexandru V.
AU - An, Fangmei
AU - Luvsanjav, Delgermaa
AU - Jin, Zhe
AU - Agarwal, Rachana
AU - Tomuleasa, Ciprian
AU - Popescu, Irinel
AU - Alexandrescu, Sorin
AU - Dima, Simona
AU - Chivu-Economescu, Mihaela
AU - Montgomery, Elizabeth A.
AU - Torbenson, Michael
AU - Meltzer, Stephen J.
AU - Selaru, Florin M.
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
KW - Gastric cancer
KW - MicroRNA-21
KW - Serpini1 gene
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U2 - 10.1016/j.dld.2012.02.016
DO - 10.1016/j.dld.2012.02.016
M3 - Article
C2 - 22464652
AN - SCOPUS:84861344982
SN - 1590-8658
VL - 44
SP - 589
EP - 596
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
IS - 7
ER -