Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer
文献类型：期刊论文
| 作者 | Peng, Yin13,14; Zhang, Xiaojing12,13,14; Lin, Huijuan10,11; Deng, Shiqi14; Qin, Ying9; He, Jieqiong14; Hu, Fan14; Zhu, Xiaohui14; Feng, Xianling14; Wang, Jian10 |
| 刊名 | AGING-US
 |
| 出版日期 | 2021-04-15 |
| 卷号 | 13期号:7页码:10749-10769 |
| ISSN号 | 1945-4589 |
| 关键词 | miRNA-150 SUFU Wnt/beta-catenin hedgehog EMT |
| 英文摘要 | Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration in vitro. We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic beta-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions in vivo, suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression. |
| 资助项目 | National Natural Science Foundation of China[31601028] ; National Natural Science Foundation of China[81772592] ; National Natural Science Foundation of China[81871969] ; Nature Science Foundation of Guangdong Province[2017A030313144] ; Nature Science Foundation of Guangdong Province[2017A030313479] ; Nature Science Foundation of Guangdong Province[2017B030301016] ; Medical science and technology research foundation of Guangdong Province[A2019211] ; Medical science and technology research foundation of Guangdong Province[A2018170] ; Shenzhen Basic Research Fund[JCYJ20170818142852491] ; Shenzhen Basic Research Fund[JCYJ20170413093358429] ; Shenzhen Basic Research Fund[JCYJ20190808163801777] ; Shenzhen University Talent program[000324] ; Startup Fund of Shenzhen University[2018015] ; High Quality University Construction 2nd phase[860-00000210] ; National Key Research and Development Program of China[2016YFB0201305] ; Youth talent support program in medical center Shenzhen University |
| WOS研究方向 | Cell Biology ; Geriatrics & Gerontology |
| 语种 | 英语 |
| 出版者 | IMPACT JOURNALS LLC |
| WOS记录号 | WOS:000657258800016 |
| 源URL | [http://119.78.100.204/handle/2XEOYT63/17535]  |
| 专题 | 中国科学院计算技术研究所期刊论文_英文 |
| 通讯作者 | Li, Song; Jin, Zhe |
| 作者单位 | 1.Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA 2.Johns Hopkins Univ, Dept Med, GI Div, Sch Med, Baltimore, MD 21287 USA 3.Shenzhen Sci & Technol Dev Exchange Ctr, Shenzhen 518060, Guangdong, Peoples R China 4.Meharry Med Ctr, Dept Med, Nashville, TN 37208 USA 5.Howard Univ, Coll Med, Canc Ctr, Washington, DC 20060 USA 6.Howard Univ, Coll Med, Dept Med, Washington, DC 20060 USA 7.Shenzhen Univ, Dept Vasc Surg, Affiliated Hosp 1, Shenzhen 518060, Guangdong, Peoples R China 8.Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518000, Guangdong, Peoples R China 9.Shenzhen Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Shenzhen 518000, Guangdong, Peoples R China 10.Guangzhou Med Univ, Dept Pathol & Pathophysiol, Guangzhou 510000, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Peng, Yin,Zhang, Xiaojing,Lin, Huijuan,et al. Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer[J]. AGING-US,2021,13(7):10749-10769. |
| APA | Peng, Yin.,Zhang, Xiaojing.,Lin, Huijuan.,Deng, Shiqi.,Qin, Ying.,...&Jin, Zhe.(2021).Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer.AGING-US,13(7),10749-10769. |
| MLA | Peng, Yin,et al."Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer".AGING-US 13.7(2021):10749-10769. |
入库方式： OAI收割
来源：计算技术研究所
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