Functional analysis of miR-375, a candidate of tumor suppressor miRNA in gastric cancer

胃癌抑癌miRNA候选物miR-375的功能分析

• 批准号: 22790349
• 负责人: TSUKAMOTO Yoshiyuki
• 金额: $ 2.5万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790349/
• 关键词: マイクロRNA; 胃癌; miR-375

In this study, we found that miRNA-375(miR-375) was the most downregulated and that its ectopic expression in gastric carcinoma cells markedly reduced cell viability via the caspase-mediated apoptosis pathway. Interestingly, we found that expression of miR-375 inhibited expression of PDK1, which is a direct target of miR-375, followed by suppression of Akt phosphorylation. Further analysis by gene expression microarray revealed that 14-3-3zeta, a potent antiapoptotic gene, was significantly downregulated at both the mRNA and protein levels in cells transfected with miR-375. The activity of a luciferase reporter containing the miR-375 binding sequence at the 3' untranslated region(UTR) of 14-3-3zeta mRNA was repressed by the ectopic expression of miR-375, suggesting that miR-375 targets the 3' UTR of 14-3-3zeta. In addition, knockdown of either PDK1 or 14-3-3zeta in gastric carcinoma cells induced caspase activation, which was also observed in miR-375-transfected cells, suggesting that miR-375 may exert its proapoptotic function, at least in part, through the downregulation of PDK1 and 14-3-3zeta. Taken together, we propose that miR-375 is a candidate tumor suppressor miRNA in gastric carcinoma

在这项研究中，我们发现miRNA-375（miR-375）是最下调的，并且其在胃癌细胞中的异位表达显着降低了通过caspase介导的凋亡途径的细胞活力。有趣的是，我们发现miR-375的表达抑制了PDK1的表达，这是miR-375的直接靶标，然后抑制Akt磷酸化。基因表达微阵列的进一步分析表明，14-3-3zeta是一种有效的抗凋亡基因，在用miR-375转染的细胞中的mRNA和蛋白质水平都显着下调。在14-3-3zeta mRNA的3'未翻译区域（UTR）上含有miR-375结合序列的荧光素酶报告基因的活性被miR-375的异位表达抑制，这表明miR-375靶向3'utr的14-3-3-3zeta。此外，胃癌细胞中PDK1或14-3-3zeta敲低诱导的caspase激活，这也在miR-375转染的细胞中观察到，这表明MiR-375至少可以通过PDK1和14-3-3zeta的下降，至少在部分中发挥其促凋亡功能。综上所述，我们提出miR-375是胃癌中的候选肿瘤miRNA

项目成果

MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta.

MicroRNA-375 在胃癌中下调，并通过靶向 PDK1 和 14-3-3zeta 来调节细胞存活。

• 发表时间: 2010
• 期刊: Cancer Res. 70
• 作者: Tsukamoto;Y
• 通讯作者: Y

胃癌におけるマイクロRNA発現

胃癌中微小RNA的表达

• 发表时间: 2011
• 作者: 成松隆弘;ほか
• 通讯作者: ほか

Overexpression of miR-210, a downstream target of HIF1α, causes centrosome amplification in renal carcinoma cells

• DOI: 10.1002/path.2860
• 发表时间: 2011-06-01
• 期刊: JOURNAL OF PATHOLOGY
• 影响因子: 7.3
• 作者: Nakada, Chisato;Tsukamoto, Yoshiyuki;Moriyama, Masatsugu
• 通讯作者: Moriyama, Masatsugu

Genomic profiling of renal cell carcinoma in patients with end-stage renal disease

• DOI: 10.1111/j.1349-7006.2011.02176.x
• 发表时间: 2012-03-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Inoue, Toru;Matsuura, Keiko;Moriyama, Masatsugu
• 通讯作者: Moriyama, Masatsugu

MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targetting PDK1 and 14-3-3zeta

MicroRNA-375 在胃癌中下调，并通过靶向 PDK1 和 14-3-3zeta 调节细胞存活

• 发表时间: 2010
• 作者: Nguyen;T.L.;Uchida;T.;Tsukamoto;Y.;Trinh;D.T.;Ta;L.;Mai;B.H.;Le;S.H.;Thai;K.D.;Ho;D.D.;et al.;塚本善之
• 通讯作者: 塚本善之