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.
胰腺导管腺癌（PDAC）是最常见的胰腺癌类型，每年导致约46.7万例癌症死亡。该疾病早期常无症状，导致诊断延迟，患者就诊时多已进展至晚期。现有治疗方案对生存期的改善有限，且仅少数患者携带可干预的基因组变异。因此，亟需为胰腺癌患者开发基于分子、细胞和功能分析的创新性个体化治疗策略。然而，目前PDAC中发现的大多数基因变异尚无法靶向治疗，或患者反应未达预期。为推进PDAC的临床诊疗，需关注非基因组生物标志物及替代性分子靶点。近期基因表达和单细胞转录组分析已鉴定出影响疾病进展和药物疗效的分子亚型及转录细胞状态。本综述将介绍长链非编码RNA（lncRNA）和RNA结合蛋白（RBP），它们能通过多种机制调控细胞转录组，从而参与疾病进展。我们将分别概述lncRNA和RBP的基本功能，重点阐述在PDAC发生发展、疾病进展及药物反应中发挥作用的特定lncRNA与RBP，最后探讨干预lncRNA和RBP表达与功能的潜在策略。
Long Non-Coding RNAs and RNA-Binding Proteins in Pancreatic Cancer Development and Progression
肿瘤(癌症)患者之家