miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer.
miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer.
复制标题
miR-135b 通过靶向结直肠癌中的转化生长因子β受体 II (TGFBR2) 促进癌症进展
DOI：
10.1371/journal.pone.0130194
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ba Y
中科院分区：
文献类型：
--
作者：
Li J;Liang H;Bai M;Ning T;Wang C;Fan Q;Wang Y;Fu Z;Wang N;Liu R;Zen K;Zhang CY;Chen X;Ba Y
转化的生长因子β（TGF-β）信号传导途径是肿瘤抑制途径，通常在结直肠癌中灭活（CRC）癌细胞下调TGFBR2的机制尚不清楚，我们发现TGFBR2蛋白水平在CRC组织中一直更新它的mRNA水平在这些组织中有所不同，表明转录后机制与TGFBR2的调节有关，因为microRNA（miRNA）是基因表达的有力的转录后调节剂。在CRC组织样品中，miR-135b和TGFBR2蛋白的水平与TGFBR2蛋白之间的相关性不是通过过表达或沉默CRC细胞中的miRNA。 TGFBR2转录本和调节TGFBR2的表达。测定法。通过抑制TGFBR2翻译，CRC中的癌基因。
The transforming growth factor beta (TGF-β) signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colorectal cancer (CRC). The inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway. However, the mechanism by which cancer cells downregulate TGFBR2 is unclear. In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that potentially target TGFBR2. We identified the specific targeting site of miR-135b in the 3’-untranslated region (3’-UTR) of TGFBR2. We further identified an inverse correlation between the levels of miR-135b and TGFBR2 protein, but not mRNA, in CRC tissue samples. By overexpressing or silencing miR-135b in CRC cells, we experimentally validated that miR-135b directly binds to the 3’-UTR of the TGFBR2 transcript and regulates TGFBR2 expression. Furthermore, the biological consequences of the targeting of TGFBR2 by miR-135b were examined using in vitro cell proliferation and apoptosis assays. We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression. Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.
登录
查看更多内容
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
人类小细胞肺癌细胞系中转化生长因子II型受体的失活。
影响因子：
8.8
作者：
Hougaard, S;Norgaard, P;Abrahamsen, N;Moses, HL;Spang-Thomsen, M;Poulsen, HS
通讯作者：
Poulsen, HS
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS
影响因子：
37.3
作者：
Bandrés E;Cubedo E;Agirre X;Malumbres R;Zárate R;Ramirez N;Abajo A;Navarro A;Moreno I;Monzó M;García-Foncillas J
通讯作者：
García-Foncillas J