Long Non-Coding RNAs in Epithelial-Mesenchymal Transition of Pancreatic Cancer

Abstract

Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.

Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies

“…More recently, circular RNAs (circRNAs) were shown to proceed differently as they prevent the inhibitory effect of miRNAs on gene expression by binding to their complementary sequences (Meyer et al, 2021). This growing, rapidly evolving field of research and its relationships with EMT in cancer have been recently reviewed (Hussen et al, 2021), and the role of the dysregulated expression of lncRNAs in the pathogenesis of aggressive cancers such as pancreatic ductal adenocarcinoma was particularly emphasized (Takahashi et al, 2021). An important point was the interplay observed between lncRNAs and the biogenesis of CSCs (McCabe and Rasmussen, 2021).…”

LncRNA PCGEM1 in Human Cancers: Functions, Mechanisms and Promising Clinical Utility

“…Mechanistically, PCGEM1 acts as a molecular sponge of miR-129-5p to upregulate ETS variant 1 (ETV1) expression ( 18 ). Epithelial-mesenchymal transition (EMT), an essential trigger of cell invasion and migration, is closely associated with cancer progression ( 67 , 68 ). Further functional assays in GC cells demonstrated that PCGEM1 promoted invasion and motility of GC cells through regulating SNAI1 ( 28 , 30 ), a transcription factor that modulates the E-cadherin/N-cadherin ratio and induces EMT ( 69 ) ( Figure 3 ).…”

Emerging Role of Epigenetic Alterations as Biomarkers and Novel Targets for Treatments in Pancreatic Ductal Adenocarcinoma

“…Several long non-coding RNAs (lncRNAs) have been shown to be involved in tumor progression in PDAC, and their detection in plasma or serum have been explored as potential biomarkers [79][80][81]. The Hox transcript antisense RNA (HOTAIR) lncRNA and hexokinase-2 (HK2) expression levels are elevated in the serum of patients with PDAC compared to healthy controls [82].…”