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

Kenji Takahashi,Kenzui Taniue,Toshikatsu Okumura,Yusuke Ono,Mikihiro Fujiya,Yusuke Mizukami

doi:10.3389/fmolb.2021.717890

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.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer
We present the roles of oncogenic and tumorsuppressive long ncRNA (lncRNA) in epithelial-mesenchymal transition (EMT) regulation in pancreatic ductal adenocarcinoma (PDAC), as well as possible strategies to utilize the lncRNAs associated with EMT to develop clinical applications for diagnosis and therapy of human PDAC
As an oncogenic lncRNA in PDAC, we previously reported that lncRNA highly upregulated in liver cancer (HULC) was exceptionally expressed in PDAC cell lines and could enhance cell invasion and migration through induction of EMT

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. In PDAC tissues, Xist is upregulated, and directly targets and attenuates the activity of miR-141-3p, which was downregulated, to enhance tumor cell invasion and migration (Sun and Zhang 2019). Sox2ot acts as a miRNA sponge to the miR-200 family, upregulates Sox2 expression, and promotes EMT and stemness, suggesting that Sox2ot can accelerate invasion and metastasis of PDAC (Li et al, 2018).

Results

Conclusion