Heliyon (Apr 2021)
MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT
- Yin Peng,
- Ying Qin,
- Xiaojing Zhang,
- Shiqi Deng,
- Yuan Yuan,
- Xianling Feng,
- Wangchun Chen,
- Fan Hu,
- Yuli Gao,
- Jieqiong He,
- Yulan Cheng,
- Yanjie Wei,
- Xinmin Fan,
- Hassan Ashktorab,
- Duane Smoot,
- Song Li,
- Stephen J. Meltzer,
- Shutong Zhuang,
- Na Tang,
- Zhe Jin
Affiliations
- Yin Peng
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518055, China; Corresponding author.
- Ying Qin
- Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518000, China
- Xiaojing Zhang
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518055, China; Department of Pathology, Guangdong Province Key Laboratory of Molecular Oncologic Pathology, China
- Shiqi Deng
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Yuan Yuan
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Xianling Feng
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Wangchun Chen
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Fan Hu
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Yuli Gao
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Jieqiong He
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Yulan Cheng
- Department of Medicine/GI Division, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA
- Yanjie Wei
- Center for High Performance Computing, Shenzhen Institutes of Advanced Technology, Shenzhen, Guangdong, 518000, China
- Xinmin Fan
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China
- Hassan Ashktorab
- Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC 20060, USA
- Duane Smoot
- Department of Medicine, Meharry Medical Center, Nashville, TN 37208, USA
- Song Li
- Shenzhen Science & Technology Development Exchange Center, Shenzhen Science and Technology Building, Shenzhen, Guangdong, 518055, China
- Stephen J. Meltzer
- Department of Medicine/GI Division, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA
- Shutong Zhuang
- Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518000, China
- Na Tang
- Department of Pathology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
- Zhe Jin
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518055, China; Corresponding author.
- Journal volume & issue
-
Vol. 7,
no. 4
p. e06695
Abstract
Previous research has found that miRNA-20b is highly expressed in gastric cancer (GC), however, its function and underlying mechanism are not clear. Wnt signaling pathway, implicated in tumorigeneisis, is activated in more than 30% of GC. We would like to characterize the biological behavior of miRNA-20b in terms of modulating Wnt/β-catenin signaling and EMT. We showed that miRNA-20b inhibitors suppressed Topflash/Fopflash dependent luciferase activity and the β-catenin nuclear translocation, resulting in inhibition of Wnt pathway activity and EMT. SUFU, negatively regulating Wnt and Hedgehog signaling pathway, was proved to be targeted by miRNA-20b. Moreover, additional knockdown of SUFU alleviated the inhibitory effect on Wnt pathway activity, EMT, cell proliferation/migration and colony formation caused by miRNA-20b inhibition.In summary, miRNA-20b is an oncogenic miRNA and promoted cell proliferation, migration and EMT in GC partially by activating Wnt pathway via targeting SUFU.
