MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer.
MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer.
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DOI：
10.1016/j.dld.2012.02.016
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发表时间：
2012-07
影响因子：
4.5
通讯作者：
Selaru, Florin M.
中科院分区：
文献类型：
--
作者：
Yamanaka, Sumitaka;Olaru, Alexandru V.;An, Fangmei;Luvsanjav, Delgermaa;Jin, Zhe;Agarwal, Rachana;Tomuleasa, Ciprian;Popescu, Irinel;Alexandrescu, Sorin;Dima, Simona;Chivu-Economescu, Mihaela;Montgomery, Elizabeth A.;Torbenson, Michael;Meltzer, Stephen J.;Selaru, Florin M.
迫切需要在分子水平上对胃癌进行深入的认识。一个重要的致癌microRNA， miR-21，先前被报道在胃癌中上调。我们利用人组织标本和MKN-28人胃癌细胞系，基于miR-21的失调，对miR-21的下游信使RNA靶点进行了无偏搜索。分子技术包括microRNA微阵列、cDNA微阵列、miR和mRNA表达的qRT-PCR、用miR-21抑制剂或serini1转染MKN-28，然后进行Western blotting、流式细胞术和荧光素酶报告细胞周期分析。这项研究确定了serpin1作为miR-21的推测靶点。荧光素酶测定显示miR-21与serini1 3'UTR之间存在直接相互作用。在胃癌的一个亚组中，MiR-21和serini1的表达水平呈负相关，这表明一种包括这两种分子的调节机制。此外，serini1诱导MKN28生长迟缓，并诱导强烈的G1/S阻滞，提示其在胃中具有潜在的肿瘤抑制功能。综上所述，这些数据表明，在胃癌的一个亚组中，miR-21上调，诱导serini1下调，serini1反过来释放G1-S过渡检查点，最终结果是肿瘤生长增加。
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. 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 MKN-28 human gastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN-28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay. 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. 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.
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影响因子：
3.7
作者：
Agarwal R;Mori Y;Cheng Y;Jin Z;Olaru AV;Hamilton JP;David S;Selaru FM;Yang J;Abraham JM;Montgomery E;Morin PJ;Meltzer SJ
通讯作者：
Meltzer SJ
影响因子：
6.2
作者：
NAKASHIMA, H;INOUE, H;AKIYOSHI, T
通讯作者：
AKIYOSHI, T
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM
DOI：
10.1073/pnas.0404432101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Calin, GA;Liu, CG;Croce, CM
通讯作者：
Croce, CM
影响因子：
6.7
作者：
Kennedy, Sarah A.;van Diepen, Angela C.;Birch, Nigel P.
通讯作者：
Birch, Nigel P.