The Role of Circular RNAs in Pancreatic Ductal Adenocarcinoma and Biliary-Tract Cancers

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) and biliary-tract cancers (BTC) often present at a late stage, and consequently patients have poor survival-outcomes. Circular RNAs (circRNAs) are non-coding RNA molecules whose role in tumourigenesis has recently been realised. They are stable, conserved and abundant, with tissue-specific expression profiles. Therefore, significant interest has arisen in their use as potential biomarkers for PDAC and BTC. High-throughput methods and more advanced bioinformatic techniques have enabled better profiling and progressed our understanding of how circRNAs may function in the competing endogenous RNA (ceRNA) network to influence the transcriptome in these cancers. Therefore, the aim of this systematic review was to describe the roles of circRNAs in PDAC and BTC, their potential as biomarkers, and their function in the wider ceRNA network in regulating microRNAs and the transcriptome. Medline, Embase, Scopus and PubMed were systematically reviewed to identify all the studies addressing circRNAs in PDAC and BTC. A total of 32 articles were included: 22 considering PDAC, 7 for Cholangiocarcinoma (CCA) and 3 for Gallbladder Cancer (GBC). There were no studies investigating Ampullary Cancer. Dysregulated circRNA expression was associated with features of malignancy in vitro, in vivo, and ex vivo. Overall, there have been very few PDAC and BTC tissues profiled for circRNA signatures. Therefore, whilst the current studies have demonstrated some of their functions in these cancers, further work is required to elucidate their potential role as cancer biomarkers in tissue, biofluids and biopsies.

CircRNA circ_0092314 Induces Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells via Elevating the Expression of S100P by Sponging miR-671

“…Over the last several years, although we should acknowledge that numerous efforts to improve the efficacy of surgery and chemotherapy in PAAD patients have been made, there are still few reliable biomarkers or effective therapeutic strategies for daily clinical practice in PAAD. Increasing evidence indicated that circRNAs have great potential to regulate cancer cell proliferation, apoptosis, invasion, EMT, metastasis and response to chemotherapy, implying that circRNAs may be used as novel potential therapeutic targets for treating various tumors including PAAD (9,10,21,22). Here, we confirmed that the knockdown of circ_0092314 suppressed the growth and invasion of PAAD cells in vitro, and resulted in reduced tumor size and tumor weight in vivo, suggesting that targeting circ_0092314 is a potential therapeutic strategy for PAAD.…”

Current Status of Functional Studies on Circular RNAs in Rheumatoid Arthritis and Their Potential Role as Diagnostic Biomarkers

“…The altered expression of circRNAs between normal and pathological conditions has been observed in numerous diseases. 22 , 23 Therefore, circRNAs (especially in PBMCs) were selected to explore the possibility of being used as biomarkers for the diagnosis of these diseases.…”

Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer

“…These features underline the requirement of developing more effective treatments for PaC. Noncoding RNAs (ncRNAs) are differentially expressed in cancer and control diverse signaling pathways involved in the regulation of therapeutic resistance [ 5 , 6 , 7 , 8 ]. An improved understanding of the relationship between therapeutic resistance and ncRNAs can provide meaningful insights to develop new treatment strategies for PaC.…”

“…For example, a recent study demonstrated that lncRNA-ADPGK-AS1 inhibits miR-205-5p, thereby promoting the progression of PaC via activating epithelial-to-mesenchymal transition (EMT) [ 13 ]. Moreover, circular RNAs (circRNAs) can control gene transcription via interaction with RNA-binding proteins [ 8 , 14 ]. They also regulate the signaling pathways through the sequestration of miRNAs [ 8 , 15 ].…”

“…Moreover, circular RNAs (circRNAs) can control gene transcription via interaction with RNA-binding proteins [ 8 , 14 ]. They also regulate the signaling pathways through the sequestration of miRNAs [ 8 , 15 ].…”