@article{730bf2d1bcbb4921b2b46997eb7e13a9,
title = "MiRNA-194 activates the Wnt/β-catenin signaling pathway in gastric cancer by targeting the negative Wnt regulator, SUFU",
abstract = "Emerging evidence has shown that miRNA-194 is aberrantly upregulated in gastric cancer (GC); however, the biological mechanisms underlying its involvement are largely unknown. Wnt/β-catenin signaling has been implicated in gastric tumorigenesis; we therefore hypothesized that miRNA-194 promotes gastric carcinogenesis by activating Wnt/β-catenin signaling. MiRNA-194 was found to be overexpressed in GC cell lines and 43 paired GC tissues. Overexpression of miRNA-194 promoted cell proliferation and migration, while inhibition of miRNA-194 blocked these processes. Inhibition of miRNA-194 decreased tumor volumes in nude mice. Furthermore, miRNA-194 inhibitors promoted cytoplasmic localization of β-catenin, leading to repression of Wnt signaling. We also discovered that SUFU, a known negative regulator of Hedgehog and Wnt signaling, was a target of miRNA-194. Anti-SUFU siRNAs rescued the inhibitory effects of miRNA-194 antagonists on cell proliferation and migration and on colony formation. We also found that SUFU expression was downregulated in GC tissues and cell lines and negatively correlated with miRNA-194 expression in primary GC tissues. Moreover, SUFU expression was negatively correlated with tumor stage, supporting its potential as a diagnostic or prognostic marker in GC. Taken together, these findings suggest that miRNA-194 is oncogenic and promotes GC cell proliferation and migration by activating Wnt signaling, at least in part, via suppression of SUFU.",
keywords = "Gastric cancer, SUFU, Wnt/β-catenin signaling pathway, miRNA-194",
author = "Yin Peng and Xiaojing Zhang and Qiang Ma and Ruibin Yan and Ying Qin and Yanqiu Zhao and Yulan Cheng and Mengting Yang and Qixiang Wang and Xianling Feng and Yong Huang and Weiling Huang and Zhenfu Zhao and Liang Wang and Yanjie Wei and Zhendan He and Xinmin Fan and Song Li and Zhe Jin and Meltzer, {Stephen J.}",
note = "Funding Information: Supported by: National Natural Science Foundation of China ( 81172282 ), the Shenzhen Peacock Plan ( KQCX20130621101141669 ), the Planned Science and Technology Project of Shenzhen ( GJHS20120621142654087 and JCYJ20140418095735574 ), the Key Laboratory Project of Shenzhen ( ZDSY20130329101130496 ), Natural Science Foundation of SZU ( 201108 and T201202 ) to Z Jin; National Natural Science Foundation of China ( 31601028 ) and China Postdoctoral Science Foundation ( 2015M582417 ) to Y Peng; National Natural Science Foundation of China ( 81302151 ), the Planned Science and Technology Project of Shenzhen ( JCYJ20160422170722474 ) and Medical Science and Technology Research Foundation of Guangdong Province ( A2016112 ) to X Zhang; the Science Technology and Innovation Committee of Shenzhen Municipality ( JCYJ20160331190123578 ), Guangdong Provincial Department of Science and Technology ( 2016B090918122 ) to Y Wei; NIH grants CA211457 , CA190040 , DK087454 , CA173390 , and an American Cancer Society Clinical Research Professorship to Stephen J. Meltzer. Dr. Meltzer is the Harry B. Myerberg-Thomas R. Hendrix Professor of Gastroenterology. Publisher Copyright: {\textcopyright} 2016 Elsevier Ireland Ltd",
year = "2017",
month = jan,
day = "28",
doi = "10.1016/j.canlet.2016.10.035",
language = "English (US)",
volume = "385",
pages = "117--127",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
}