Long noncoding RNA LINC00657 enhances the malignancy of pancreatic ductal adenocarcinoma by acting as a competing endogenous RNA on microRNA-433 to increase PAK4 expression.

A long noncoding RNAs (lncRNA) called is dysregulated and contributes to tumor progression in a number of human cancer types. However, there is limited information on the expression profile and functions of in pancreatic ductal adenocarcinoma (PDAC). The expression profile of in PDAC was estimated by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). The effects of upregulation on PDAC cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo were explored using CCK-8, flow cytometry, Transwell migration and invasion assays, and a xenograft tumor formation experiment, respectively. The results revealed that was evidently upregulated in the PDAC tumors and cell lines. High expression significantly correlated with the pathological T stage, lymph node metastasis, and shorter overall survival. Functional analysis demonstrated that knockdown inhibited the proliferation, migration, and invasion while promoted the apoptosis of PDAC cells. In addition, knockdown markedly suppressed tumor growth of these cells in vivo. In terms of the mechanism, could directly interact with microRNA-433 (miR-433) and effectively worked as an miR-433 sponge, thus decreasing the competitive binding of miR-433 to mRNA and ultimately increasing PAK4 expression. The actions of knockdown on malignant phenotype of PDAC cells were strongly attenuated by miR-433 inhibition and PAK4 restoration. These results indicate that promotes PDAC progression by increasing the output of the miR-433-PAK4 regulatory loop, thus highlighting the importance of the -miR-433-PAK4 network in PDAC pathogenesis.