Long Noncoding RNA MIR600HG Binds to MicroRNA-125a-5p to Prevent Pancreatic Cancer Progression Via Mitochondrial Tumor Suppressor 1-Dependent Suppression of Extracellular Regulated Protein Kinases Signaling Pathway.

Abstract

Significance of long noncoding RNAs in pancreatic cancer (PC) progression has been documented. Here, we identified a novel long noncoding RNA MIR600HG in PC and its underlying mechanism during PC progression. Through bioinformatics analysis, we selected MIR600HG, microRNA-125a-5p (miR-125a-5p), and mitochondrial tumor suppressor 1 (MTUS1) as objects with their expression patterns assayed in the collected PC tissues and PC cells. Pancreatic cancer cells were manipulated with ectopic expression and deficiency of MIR600HG, miR-125a-5p, and/or MTUS1 for assaying cell biological processes in vitro and tumorigenesis in vivo. MIR600HG and MTUS1 levels were downregulated and miR-125a-5p was upregulated in PC tissues and cells. MIR600HG could bind to miR-125a-5p, while miR-125a-5p negatively targeted MTUS1. MIR600HG resulted in suppression in malignant properties of PCs. All these changes could be reversed by miR-125a-5p elevation. In addition, miR-125a-5p targeted MTUS1 to activate the extracellular regulated protein kinases signaling pathway. In vivo experiment also verified the inhibitory role of MIR600HG in PC. Taken together, MIR600HG acts as an inhibitor for PC progression by upregulating miR-125a-5p-mediated MTUS1 through extracellular regulated protein kinases pathway.