Silencing long noncoding RNA LINC01133 suppresses pancreatic cancer through regulation of microRNA-1299-dependent IGF2BP3.

Abstract

The deregulation of long noncoding RNAs (lncRNAs) holds great potential in the treatment of multiple cancers, including pancreatic cancer (PC). However, the specific molecular mechanisms by which LINC01133 contributes to pancreatic cancer remain unknown. Subsequent to bioinformatics analysis, we predicted and analyzed differentially expressed lncRNAs, microRNAs, and genes in pancreatic cancer. We determined the expression patterns of LINC01133, miR-1299, and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in pancreatic cancer cells, and validated their interactions through luciferase reporter and RNA immunoprecipitation assays. We implemented loss-of-function and gain-of-function experiments for LINC01133, miR-1299, and IGF2BP3 to assay their potential effects on pancreatic cancer cell functions. We observed high expression of LINC01133 and IGF2BP3, but low expression of miR-1299, in pancreatic cancer cells. Furthermore, we found that LINC01133 enhances IGF2BP3 through binding with miR-1299. Silencing LINC01133 or IGF2BP3 and/or overexpressing miR-1299 limited pancreatic cancer cell proliferation, invasion, epithelial-mesenchymal transition, and suppressed tumorigenic abilities in mice lacking T cells (nude mice). Overall, our findings identified that silencing LINC01133 downregulates IGF2BP3 by upregulating miR-1299 expression, ultimately leading to the prevention of pancreatic cancer.