SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer
Authors: Song Li
Xinmin Fan
Ruibin Yan
Zhe Jin
Xianling Feng
Wangchun Chen
Stephen J Meltzer
Yanqiu Zhao
Yulan Cheng
Xiaojing Zhang
Hassan Ashktorab
Huijuan Lin
Yanjie Wei
Shiqi Deng
Jian Wang
Yin Peng
Ying Qin
Fan Hu
Yuan Yuan
Duane Smoot
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EMT; SUFU negative regulator of hedgehog signaling; Wnt/β-catenin; miRNA-324-5p.
Affiliations: Guangdong Key Laboratory for Genome Stability & Disease Prevention, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine , Shenzhen, Guangdong, China., Department of Pathology, Guangdong Province Key Laboratory of Molecular Oncologic Pathology , Guangzhou, Guangdong, China., Department of Pathology and Pathophysiology, Guangzhou Medical University , Guangzhou, Guangdong, China., Department of Ultrasound, Guangdong Women and Children Hospital , Guangzhou, Guangdong, China., Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital , Shenzhen, Guangdong, China., Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University , Shenzhen, Guangdong, P.R. China., Department of Medicine/GI Division, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD, USA., Center for High Performance Computing, Shenzhen Institutes of Advanced Technology , Shenzhen, Guangdong, P.R. China., Department of Medicine and Cancer Center, Howard University, College of Medicine , Washington, USA., Department of Medicine, Meharry Medical Center , Nashville, TN, USA.

Abstract:  The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/β-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed in vivo and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer. 

Retracted: No

PubPeer comments:
 The fact that they choose to correct a manipulated paper says a lot about the seriousness of the publisher Taylor Francis. Figure 3F: A Western blot band (N-cadherin) has been rused from Figure 3E, rotated and presented as something else. A Western blot band (GAPDH) has been reused from Figure 4A and presented as something else. Figure 6B: A micrographs has been duplicated and presented as something else. Figure 6C: A micrograph has been duplicated from an earlier publication (Zhang, X et al., 2018; Cell Death Dis), rotated and presented as something else. ![file] ![file] ,