MiR-21-5p Induces Pyroptosis in Colorectal Cancer via TGFBI.
MiR-21-5p Induces Pyroptosis in Colorectal Cancer via TGFBI.
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DOI：
10.3389/fonc.2020.610545
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发表时间：
2020
影响因子：
4.7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Jiang R;Chen X;Ge S;Wang Q;Liu Y;Chen H;Xu J;Wu J
上睑下垂是真核细胞中一种独特的程序性细胞死亡，在癌症相关研究中引起了越来越多的关注。此外，虽然已有研究报道miR-21在结直肠癌中异常表达，但由于缺乏对miR-21转录调控机制的深入研究，其临床应用仍然有限。据我们所知，我们的研究是第一次比较miR-21-3p和miR-21-5p的临床表现和实验室表型。在形态上，将miR-21-3p或miR-21-5p抑制剂以及miR-21-5p模拟物导入HCT-116和HT-29细胞，可诱导细胞死亡。令人惊讶的是，miR-21-5p的过度表达比它的敲除更能诱导细胞死亡。对miR-21-5p过度表达的机制研究表明，包括IL-1、β和IL-18在内的各种炎症因子被释放，而与上睑下垂相关的mRNAs表达上调，蛋白质被激活。此外，miR-21-5p被发现作为下游因子对转化生长因子β诱导的转化生长因子1(TGFB1)进行显著和直接的调节。具体地说，miR-21-5p的过表达导致TGFBI表达下调，这可能是导致上睑下垂的原因。总之，我们揭示了miR-21-5p通过TGFBI调控诱导结直肠癌下垂，从而为其抗肿瘤作用提供了重要的机制见解，并扩大了其临床应用的潜力。
Pyroptosis is a distinct form of programmed cell death in eukaryotic cells that has garnered increasing attention in cancer-related research. Moreover, although miR-21 has been reported as abnormally expressed in colorectal cancer, due to a lack of in-depth research on the transcriptional regulation mechanisms of miR-21, its clinical usage remains limited. Our study is the first, to our knowledge, to compare the clinical manifestations and laboratory phenotypes associated with miR-21-3p and miR-21-5p. Morphologically, the transfection of miR-21-3p or miR-21-5p inhibitors, as well as miR-21-5p mimics into HCT-116 and HT-29 cell lines, induced cell death. Surprisingly, overexpression of miR-21-5p induced cell death more strongly than its knockdown. Mechanistic studies of miR-21-5p overexpression revealed that various inflammatory factors including IL-1β and IL-18 were released, while pyroptosis-associated mRNAs were upregulated and proteins were activated. Moreover, miR-21-5p was found to act as a downstream factor to significantly and directly regulate transforming growth factor beta-induced (TGFB1). Specifically, miR-21-5p overexpression caused downregulation of TGFBI, which may have led to pyroptosis. Collectively, we revealed that miR-21-5p induces pyroptosis in colorectal cancer via TGFBI regulation, thereby providing important mechanistic insights into its antitumor effects and expanding its potential for clinical applications.
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DOI：
10.1126/science.aaf7532
发表时间：
2016-11-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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Flavell RA
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DOI：
10.1038/nrc3932
发表时间：
2015-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Lin S;Gregory RI
通讯作者：
Gregory RI
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影响因子：
3.1
作者：
Jiang Z;Yao L;Ma H;Xu P;Li Z;Guo M;Chen J;Bao H;Qiao S;Zhao Y;Shen J;Zhu M;Meyers C;Ma G;Xie C;Liu L;Wang H;Zhang W;Dong Q;Shen H;Lin Z
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Lin Z
DOI：
10.1073/pnas.1016814108
发表时间：
2010-12-14
影响因子：
11.1
作者：
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通讯作者：
Flavell, Richard A.
不同的miR-21-3p亚型及其在结直肠癌中的不同特征
影响因子：
6.4
作者：
Jiao, Weijuan;Leng, Xueqin;Li, Jianming
通讯作者：
Li, Jianming