Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer

Peng,Yin; Zhang,Xiaojing; Lin,Huijuan; Deng,Shiqi; Huang,Yong; Qin,Ying; Feng,Xianling; Yan,Ruibin; Zhao,Yanqiu; Cheng,Yulan; Wei,Yanjie; Wang,Jian; Chen,Wangchun; Fan,Xinmin; Ashktorab,Hassan; Smoot,Duane; Meltzer,Stephen J.; Li,Song; Zhang,Zhong; Jin,Zhe

doi:10.3892/or.2018.6773

Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer

Authors:
- Yin Peng
- Xiaojing Zhang
- Huijuan Lin
- Shiqi Deng
- Yong Huang
- Ying Qin
- Xianling Feng
- Ruibin Yan
- Yanqiu Zhao
- Yulan Cheng
- Yanjie Wei
- Jian Wang
- Wangchun Chen
- Xinmin Fan
- Hassan Ashktorab
- Duane Smoot
- Stephen J. Meltzer
- Song Li
- Zhong Zhang
- Zhe Jin
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Affiliations: Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, P.R. China, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, P.R. China, Department of Pathology and Pathophysiology, The Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China, Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518000, P.R. China, Laboratory of Chemical Genomics, The Shenzhen Graduate School of Peking University, Shenzhen, Guangdong 518055, P.R. China, Department of Medicine/GI Division, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA, Center for High Performance Computing, Shenzhen Institutes of Advanced Technology, Shenzhen, Guangdong 518000, P.R. China, Department of Pathology and Pathophysiology, The Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China, Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC 20060, USA, Department of Medicine, Meharry Medical Center, Nashville, TN 37208, USA, Department of Pathology, College of Basic Medical Sciences, Shenyang Medical College, Shenyang, Liaoning 110034, P.R. China
Published online on: October 8, 2018 https://doi.org/10.3892/or.2018.6773
Pages: 3323-3334
Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A mounting body of evidence has revealed that microRNAs (miRs) serve pivotal roles in various developmental processes, and in tumourigenesis, by binding to target genes and subsequently regulating gene expression. Continued activation of the Wnt/β‑catenin signalling is positively associated with human malignancy. In addition, miR‑194 dysregulation has been implicated in gastric cancer (GC); however, the molecular mechanisms underlying the effects of miR‑194 on GC carcinogenesis remain to be elucidated. The present study demonstrated that miR‑194 was upregulated in GC tissues and SUFU negative regulator of Ηedgehog signaling (SUFU) was downregulated in GC cell lines. Subsequently, inhibition of miR‑194 attenuated nuclear accumulation of β‑catenin, which consequently blocked Wnt/β‑catenin signalling. In addition, the cytoplasmic translocation of β‑catenin induced by miR‑194 inhibition was mediated by SUFU. Furthermore, genes associated with the Wnt/β‑catenin signalling pathway were revealed to be downregulated following inhibition of the Wnt signalling pathway by miR‑194 suppression. Finally, the results indicated that cell apoptosis was markedly increased in response to miR‑194 inhibition, strongly suggesting the carcinogenic effects of miR‑194 in GC. Taken together, these findings demonstrated that miR‑194 may promote gastric carcinogenesis through activation of the Wnt/β‑catenin signalling pathway, making it a potential therapeutic target for GC.

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