Aberrantly expressed miR-188-5p promotes gastric cancer metastasis by activating Wnt/β-catenin signaling
Authors: Xiaoli Yan
Yun Li
Liying Lin
Jiajian Shi
Yun He
Jie Xu
Wannan Chen
Xinjian Lin
Xu Lin
Journal: BMC Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: Gastric cancer; Metastasis; MiR-188-5p; Wnt/β-catenin signaling.
Affiliations: Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China., Institute of Tissue Transplantation and Immunology and Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China., Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China., Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China. ., Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. .

Abstract:  Background: Gastric cancer (GC) is one of the most common human cancers with the high rate of recurrence, metastasis and mortality. Aberrantly expressed microRNAs (miRNAs) are associated with invasion and metastasis in various human cancers. Recently, miR-188-5p has been indicated as an oncogene in GC since it promotes GC cell growth and metastasis. However, the underlying molecular mechanism remains to be fully defined. Methods: Using Significance Analysis of Microarrays (SAM) screening, we identified that miR-188-5p is associated with overall survival and lymph node metastasis in patients with GC. The functional impact of miR-188-5p on GC metastasis was validated using in vitro and in vivo assays. The regulatory function of miR-188-5p on Wnt/β-catenin signaling activation through directly targeting PTEN was proven using quantitative real-time PCR, western blot analysis, a dual-luciferase assay, a Transwell assay, and immunofluorescence. Immunohistochemical analyses further confirmed the clinical significance of miR-188-5p in GC. Results: MiR-188-5p diminishes tumor suppressor PTEN expression, and further increases phospho-Ser9 of GSK3β to activate Wnt/β-catenin signaling in GC. Consequently, miR-188-5p enhanced the migration and invasion of GC cells in vitro and tumor metastasis in vivo, whereas inhibition of miR-188-5p had the opposite effects. Moreover, miR-188-5p was negatively correlated with PTEN expression but positively correlated with nuclear β-catenin staining in GC samples. Conclusions: Our findings revealed a model of the miR-188-5p-PTEN-β-catenin axis in GC, which mediates the constitutive activation of Wnt/β-catenin signaling and promotes tumor metastasis, inferring that miR-188-5p is a potential therapeutic target to treat GC. 

Retracted: No

PubPeer comments:
 The migration invasion assays of this paper have what appear to be numerous image duplications or partial image duplications. Some of these may have been treated the same (its a little unclear what the  NC miRNA used is), but some are definitely given different treatments. For example in figure 3E and 2C, in the invasion assay of the AGS cells, the same partial image is labeled as both NC and mir-188-5p mimic (light gray boxes). ![file] , 
 Dear PUBPEER administrator, Thank you very much for your email notice of July 23, 2020 regarding image duplication errors identified in our article published in BMC Cancer 19(1):505, 2019; DOI: https: doi.org 10.1186 s12885-019-5731-0. Upon receipt of your comment, we have responded immediately by sending an erratum where all the indicated errors were corrected to the journal waiting for the correction to be published. We have done a thorough investigation into the mistake and identified that there was an inadvertent mistake made in the process of transferring data pictures taken from the microscopy system. We are most grateful to PUBPEER for careful review of our paper and for noting these errors. Warmest regards, Xu Lin and Xinjian Lin Professor of Medicine Fujian Medical University ,