A novel feedback loop between high MALAT-1 and low miR-200c-3p promotes cell migration and invasion in pancreatic ductal adenocarcinoma and is predictive of poor prognosis
Authors: Liwei Wang
Jiujie Cui
Feng Jiao
Meng Zhuo
Cuncun Yuan
Ting Han
Journal: BMC Cancer (2018)
Discipline: CLINICAL MEDICINE
Keywords: Feedback loop; Metastasis-associated lung adenocarcinoma transcript 1; Pancreatic ductal adenocarcinoma; ZEB1; miR-200c-3p.
Affiliations: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China., Department of Pathology, Eye Ear Nose and Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China., Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China. .

Abstract:  Background: It was demonstrated that long non-coding RNAs occupied an important position in tumor pathogenesis and progression. We have previously found that the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) promotes cell proliferation and metastases in pancreatic ductal adenocarcinoma (PDAC). The present study was aimed to discuss the underlying mechanisms. Methods: Bioinformatics method was used to identify the miRNA target of MALAT-1. Expressions of relative genes were assessed by quantitative real-time PCR and western blotting, respectively. Sulforhodamine B assay and Transwell assay were employed to detect cell proliferation, migration and invasion, respectively. Moreover, RNA immunoprecipitation was performed to determine whether RNA-induced silencing complex contained MALAT-1 and its potential binding miRNA. Luciferase assays was used to confirm potential binding site. Results: Bioinformatics search predicted that miR-200c-3p was a direct target of MALAT-1. Further, we found a reciprocal suppression between MALAT-1 and miR-200c-3p expression. In terms of mechanisms, high MALAT-1 and low miR-200c-3p may form a novel feedback loop. On the one hand, MALAT-1 functioned as a competing endogenous RNA to suppress miR-200c-3p expression, leading to upregulation of ZEB1 expression. On the other hand, miR-200c-3p inhibited the level of MALAT-1 expression was in a way similar to miRNA-mediated downregulation of target genes. Clinical data further indicated that MALAT-1 and ZEB1 expression was negatively correlated with miR-200c-3p transcript level of PDAC tissues. There was a positive correlation between MALAT-1 and ZEB1 level. MALAT-1 (high)/miR-200c-3p (low) correlated with shorter overall survival of PDAC patients. Multivariate analysis revealed that both MALAT-1 and miR-200c-3p levels were independent prognostic factors. Conclusion: Our findings firstly revealed a novel feedback loop between high MALAT-1 and low miR-200c-3p. Targeting the feedback loop between high MALAT-1 and low miR-200c-3p will be a therapeutic strategy for PDAC. 

Retracted: No

PubPeer comments:
 This paper is one of 30+ papers by the same research group that all share the same photo. In all papers, this photo is used as a zoomed-in inset representing the high-resolution transmission electron microscopy (HRTEM) analysis of the  atomic lattice fringe and particle size of the nanoparticles. Of concern, the same photo is used to represent a different type of nanoparticle in each of these papers. Here is a collage of 6 different uses of the same photo,  Inset 1 : ![file] A list of the first 30 papers that all use this photo, and the different types of nanoparticles that they represent can e.g. be found here: * Betuu0308l Su0327en et al. - DOI: 10.1016 j.ijhydene.2018.03.175 - https: pubpeer.com publications 8AD71F4A32472314CCE9983D47E36F Here is Figure 2 of this paper that includes the  Inset 1 photo: ![file] ,