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

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

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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 AAA EXCLUSIVE 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 One-of-a-kind Hair-On Hides 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.