MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer.
MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer.
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MiR-17-5p 通过靶向转化生长因子-β 受体 2 调节胃癌中的细胞增殖和迁移
DOI：
10.18632/oncotarget.8946
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Ba Y
中科院分区：
文献类型：
--
作者：
Qu Y;Zhang H;Duan J;Liu R;Deng T;Bai M;Huang D;Li H;Ning T;Zhang L;Wang X;Ge S;Zhou L;Zhong B;Ying G;Ba Y
转化生长因子β受体2（TGFBR2）作为转化生长因子β信号通路的初始调节因子，其表达缺失或减少会导致细胞生长和侵袭失控。TGFBR2在胃癌的发生和恶性进程中起着至关重要的作用，但其机制尚不清楚。在本研究中，我们发现胃癌组织中TGFBR2蛋白水平持续上调，而TGFBR2 mRNA水平在这些组织中存在差异，这表明存在一种转录后机制参与TGFBR2的调控。已知微小RNA（miRNAs）在转录后水平调控基因表达。因此，我们进行了生物信息学分析以寻找可能靶向TGFBR2的miRNAs。发现miR - 17 - 5p与TGFBR2 mRNA的3′非翻译区（3′UTR）结合，并通过报告基因实验进一步验证了这种特异性结合。在胃癌组织中观察到miR - 17 - 5p与TGFBR2蛋白呈负相关。细胞研究表明，miR - 17 - 5p通过直接与TGFBR2 mRNA的3′UTR结合，负向调控TGFBR2的表达，从而促进细胞生长和迁移。我们还使用小干扰RNA（siRNA）和过表达质粒验证了TGFBR2的作用。我们的研究结果表明，在胃癌中存在由miR - 17 - 5p和TGFBR2介导的新型调控网络，并可能提示TGFBR2可作为胃癌的一个新的治疗靶点。
TGFBR2 serves as an initial regulator of the TGF-β signaling pathway, and loss or reduction of its expression leads to uncontrolled cell growth and invasion. TGFBR2 plays a crucial role in the carcinogenesis and malignant process of gastric cancer, but the mechanism remains unclear. In this study, we found that TGFBR2 protein levels were consistently upregulated in gastric cancer tissues, whereas TGFBR2 mRNA levels varied among these tissues, indicating that a post-transcriptional mechanism is involved in the regulation of TGFBR2. MiRNAs are known to regulate gene expression at the post-transcriptional level. Therefore, we performed bioinformatics analyses to search for miRNAs potentially targeting TGFBR2. MiR-17-5p was found to bind to the 3′UTR of TGFBR2 mRNA, and further validation of this specific binding was performed through a reporter assay. An inverse correlation between miR-17-5p and TGFBR2 protein was observed in gastric cancer tissues. Cell studies revealed that miR-17-5p negatively regulated TGFBR2 expression by directly binding to the 3′UTR of TGFBR2 mRNA, thereby promoting cell growth and migration. We also validated the role of TGFBR2 using siRNA and an overexpression plasmid. The results of our study suggest a novel regulatory network in gastric cancer mediated by miR-17-5p and TGFBR2 and may indicate that TGFBR2 could serve as a new therapeutic target in gastric cancer.
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