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

doi:10.1016/j.heliyon.2021.e06695

MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT

Heliyon. 2021 Apr 12;7(4):e06695. doi: 10.1016/j.heliyon.2021.e06695. eCollection 2021 Apr.

Authors

Yin Peng^{1

2}, Ying Qin³, Xiaojing Zhang^{1

2

4}, Shiqi Deng¹, Yuan Yuan¹, Xianling Feng¹, Wangchun Chen¹, Fan Hu¹, Yuli Gao¹, Jieqiong He¹, Yulan Cheng⁵, Yanjie Wei⁶, Xinmin Fan¹, Hassan Ashktorab⁷, Duane Smoot⁸, Song Li⁹, Stephen J Meltzer⁵, Shutong Zhuang³, Na Tang¹⁰, Zhe Jin^{1

2}

Affiliations

¹ Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China.
² Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518055, China.
³ Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518000, China.
⁴ Department of Pathology, Guangdong Province Key Laboratory of Molecular Oncologic Pathology, China.
⁵ Department of Medicine/GI Division, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA.
⁶ Center for High Performance Computing, Shenzhen Institutes of Advanced Technology, Shenzhen, Guangdong, 518000, China.
⁷ Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC 20060, USA.
⁸ Department of Medicine, Meharry Medical Center, Nashville, TN 37208, USA.
⁹ Shenzhen Science & Technology Development Exchange Center, Shenzhen Science and Technology Building, Shenzhen, Guangdong, 518055, China.
¹⁰ 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.

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.

Keywords: EMT; SUFU; Wnt/β-catenin; miRNA-20b.

Grants and funding

U54 MD007597/MD/NIMHD NIH HHS/United States