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| Content Provider | frontiers |
|---|---|
| Author | Ye, Jun Lei, Jiacai Fang, Qingqing Shen, Yimin Xia, Wenjie Hu, Xiaoge Xu, Qiuran Yuan, Hongjun Huang, Jian Ni, Chao |
| Abstract | Quiescent caner stem cells are identified as a subpopulation of colon cancer cells in dormant state and possess strong stem-cell like characteristics. Previously, we have identified this subpopulation in colorectal cancer (quiescent colon cancer stem cells, QCCSCs), and find QCCSCs are sensitive to the apoptotic effect of IFN-γ, which is attributed to their high IFN-γR expression levels. Microarray and bioinformatic analysis indicate miR-4666-3p is low expressed in QCCSCs and target IFN-γR1/2, which is proved by luciferase assay and western-blot. Furthermore, we find miR-4666-3p could also target TGF-βR1 to block the activation of TGF-β1/Smad pathway, therefore function as a tumor suppressor gene to inhibit the stemness of colon cancer cells. Besides, compared with QCCSCs, we find the TGF-β1 expression also decreased with the weakening of stemness properties. In terms of mechanism, our result reveal TGF-β1 is the target gene of miR-329, which is also high expressed in non-QCCSCs. Thereafter, we perform gain- and loss- function experiments to confirm the synergistic effect between miR-4666-3p and miR-329 in blocking the activation of TGF-β/Smad pathway. Finally, we evaluate the expression of both miR-4666-3p and miR-329 in 73 tumor specimens and paired normal tissue, and find both two miRNAs are related to unfavorable prognosis and advanced tumor stage in colorectal cancer. Our study revealed a novel epigenetic regulation mechanism in colon cancer stem cells, which could be exploited as a novel therapeutic strategy for cancer treatment. |
| ISSN | 2234943X |
| DOI | 10.3389/fonc.2019.01251 |
| Volume Number | 9 |
| Journal | Frontiers in Oncology |
| Language | English |
| Publisher Date | 2019-11-19 |
| Access Restriction | Open |
| Subject Keyword | MiR-4666-3p MiR-329 Colorectal cancer Cancer stem cells TGF-β/Smad |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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