MicroRNA-383 acts as a tumor suppressor in colorectal cancer by modulating CREPT/RPRD1B expression.
MicroRNA-383 acts as a tumor suppressor in colorectal cancer by modulating CREPT/RPRD1B expression.
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MicroRNA-383 通过调节 CREPT/RPRD1B 表达作为结直肠癌肿瘤抑制因子
DOI：
10.1002/mc.22866
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发表时间：
2018-10
影响因子：
4.6
通讯作者：
Chang Z
中科院分区：
文献类型：
--
作者：
Li J;Smith AR;Marquez RT;Li J;Li K;Lan L;Wu X;Zhao L;Ren F;Wang Y;Wang Y;Jia B;Xu L;Chang Z
CREPT（肿瘤中细胞周期相关和表达升高的蛋白）/RPRD1B 是一种在肿瘤发生过程中增强 Cyclin D1 转录以促进细胞增殖的新型蛋白，已被证明在大多数肿瘤中高表达。然而，目前尚不清楚 CREPT 在结直肠癌中如何受到调节。在这项研究中，我们报告 miR-383 负向调节 CREPT 表达。我们观察到结肠癌细胞系和结肠肿瘤组织中 CREPT 表达上调，但 miR-383 表达下调。有趣的是，我们发现 miR-383 的强制表达在 mRNA 和蛋白质水平上抑制了 CREPT 的表达。使用荧光素酶报告基因，我们发现 miR-383 直接靶向 CREPT mRNA 的 3'-UTR。我们一致观察到，miR-383 的过度表达缩短了多种结直肠癌细胞中 CREPT mRNA 的半衰期。此外，miR-383的恢复抑制了结肠癌细胞的生长和集落形成，同时抑制了CREPT和相关下游基因的表达。最后，我们证明结肠癌细胞中 miR-383 的稳定过度表达可降低肿瘤的生长。我们的结果表明，结直肠癌中 CREPT 的大量表达归因于 miR-383 水平的降低。这项研究为使用引入的 miRNA 治疗结直肠癌的潜在治疗策略提供了新的思路。
CREPT (Cell-cycle-related and expression-elevated protein in tumor)/RPRD1B, a novel protein that enhances the transcription of Cyclin D1 to promote cell proliferation during tumorigenesis, was demonstrated highly expressed in most of tumors. However, it remains unclear how CREPT is regulated in colorectal cancers. In this study, we report that miR-383 negatively regulates CREPT expression. We observed that CREPT was up-regulated but the expression of miR-383 was down regulated in both colon cancer cell lines and colon tumortissues. Intriguingly,we found that enforced expression of miR-383 inhibited the expression of CREPT at both the mRNA and protein level. Using a luciferase reporter, we showed that miR-383 targeted the 3′-UTR of CREPT mRNA directly. Consistently we observed that over expression of miR-383 shortened the half-life of CREPT mRNA in varieties of colorectal cancer cells. Furthermore, restoration of miR-383 inhibited cell growth and colony formation of colon cancer cells accompanied by inhibition of expression of CREPT and related downstream genes. Finally, we demonstrated that stable over expression of miR-383 in colon cancer cells decreased the growth of the tumors. Our results revealed that the abundant expression of CREPT in colorectal cancers is attributed to the decreased level of miR-383. This study shed a new light on the potential therapeutic therapy strategy for colorectal cancers using introduced miRNA.
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影响因子：
--
作者：
Smith AR;Marquez RT;Tsao WC;Pathak S;Roy A;Ping J;Wilkerson B;Lan L;Meng W;Neufeld KL;Sun XF;Xu L
通讯作者：
Xu L
DOI：
10.1016/j.bbagrm.2012.10.003
发表时间：
2013-01
影响因子：
4.7
作者：
Mischo, Hannah E.;Proudfoot, Nick J.
通讯作者：
Proudfoot, Nick J.
影响因子：
4.4
作者：
Hu Z
通讯作者：
Hu Z
影响因子：
50.3
作者：
Lu, Dongdong;Wu, Yinyuan;Chang, Zhijie
通讯作者：
Chang, Zhijie
影响因子：
4
作者：
Jung, Hyun Min;Choi, Seong-Jun;Kim, Jin Kyeoung
通讯作者：
Kim, Jin Kyeoung