Non-coding RNAs in pancreatic ductal adenocarcinoma: New approaches for better diagnosis and therapy

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with a 5-year survival rate less than 8%, which has remained unchanged over the last 50 years. Early detection is particularly difficult due to the lack of disease-specific symptoms and a reliable biomarker. Multimodality treatment including chemotherapy, radiotherapy (used sparingly) and surgery has become the standard of care for patients with PDAC. Carbohydrate antigen 19-9 (CA 19-9) is the most common diagnostic biomarker; however, it is not specific enough especially for asymptomatic patients. Non-coding RNAs are often deregulated in human malignancies and shown to be involved in cancer-related mechanisms such as cell growth, differentiation, and cell death. Several micro, long non-coding and circular RNAs have been reported to date which are involved in PDAC. Aim of this review is to discuss the roles and functions of non-coding RNAs in diagnosis and treatments of PDAC.

Keywords: Circular RNA; Long non-coding RNA; MicroRNA; Non-coding RNAs; Pancreatic ductal adenocarcinoma.

Graphical abstract

Fig. 1

Involvement of miRs in PDAC progression. miRs are classified both as oncogenes and tumour suppressors by moderating several key downstream gene targets which control different cellular and biological processes involved in cancer progression.

Fig. 2

Venn diagram shows the overlap between differentially expressed miRs in different lesions of PDAC. It can be noted that miR-21, miR-155, miR-145 and miR-296–5p are presented in all PanIN lesions, while miR-200a/b in both PanIN-I and II. miR-221 are detected only in PanIN-I and III.

Fig. 3

Biological processes and their related ncRNAs involved in PDAC progression. Both lncRNAs and miRs are aberrantly expressed in several biological processes during PDAC development including metastasis, cell proliferation, invasion, homoeostasis, migration, autophagy, hypoxia, apoptosis, cell cycle arrest, EMT, lipogenesis and angiogenesis. miR-21 is the most known oncogenic miR and is involved in both cell proliferation and apoptosis, while a well-described lncRNA known as HOTAIRM1 contributes to migration, apoptosis and cell cycle arrest.

Fig. 4

Biological processes and their related circRNAs involved in PDAC development. circRNAs are also linked to several biological processes, which are related to PDAC progression. Especially, aberrant expression of these ncRNAs subtype is associated with invasion, metastasis, angiogenesis, tumorigenesis, migration, proliferation. ciRS-7 is a well-known circRNA, which is highly correlated to angiogenesis, invasion and proliferation, while circRHOT1 with invasion, metastasis and proliferation.

Fig. 5

Role of lncRNAs with their target miRs in PDAC therapy. Interactions between miRs and lncRNAs have prompted novel therapeutic strategies for PDAC. Specifically, MALAT1, PVT1 and HOTAIR together with their target miRs could be used for the prediction of gemcitabine-based chemotherapy efficacy as first-line treatment of PDAC patients.