Long non-coding RNAs and RNA-binding proteins in pancreatic cancer development and progression

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is responsible for about 467,000 cancer deaths annually. An oftentimes asymptomatic early phase of this disease results in a delayed diagnosis, and patients often present with advanced disease. Current treatment options have limited survival benefits, and only a minor patient population carries actionable genomic alterations. Hence, innovative personalized treatment strategies that consider molecular, cellular and functional analyses are urgently needed for pancreatic cancer patients. However, the majority of the genetic alterations found in PDAC are currently undruggable, or patients’ response is not as expected. Therefore, non-genomic biomarkers and alternative molecular targets should be considered in order to advance the clinical management of PDAC patients. In line with this, recent gene expression and single-cell transcriptome analyses have identified molecular subtypes and transcriptional cell states that affect disease progression and drug efficiency. In this review, we will introduce long non-coding RNAs (lncRNAs) as well as RNA-binding proteins (RBPs) that are able to modulate the transcriptome of a cell through diverse mechanisms, thereby contributing to disease progression. We will provide a brief overview about the general functions of lncRNAs and RBPs, respectively. Subsequently, we will highlight selected lncRNAs and RBPs that have been shown to play a role in PDAC development, progression and drug response. Finally, we will present strategies aiming to interfere with the expression and function of lncRNAs and RBPs.