miRNAs in pancreatic cancer progression and metastasis

Abstract

Small non-coding RNA or microRNA (miRNA) are critical regulators of eukaryotic cells. Dysregulation of miRNA expression and function has been linked to a variety of diseases including cancer. They play a complex role in cancers, having both tumour suppressor and promoter properties. In addition, a single miRNA can be involved in regulating several mRNAs or many miRNAs can regulate a single mRNA, therefore assessing these roles is essential to a better understanding in cancer initiation and development. Pancreatic cancer is a leading cause of cancer death worldwide, in part due to the lack of diagnostic tools and limited treatment options. The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), is characterised by major genetic mutations that drive cancer initiation and progression. The regulation or interaction of miRNAs with these cancer driving mutations suggests a strong link between the two. Understanding this link between miRNA and PDAC progression may give rise to novel treatments or diagnostic tools. This review summarises the role of miRNAs in PDAC, the downstream signalling pathways that they play a role in, how these are being used and studied as therapeutic targets as well as prognostic/diagnostic tools to improve the clinical outcome of PDAC.

Dysregulation of a Subset of Circulating and Vesicle-Associated miRNA in Pancreatic Cancer

“…Furthermore, the selected second set of miRNAs included miRNAs with an oncogenic role, or generally upregulated in human tumors, and miRNAs with a tumor suppressor function, or generally downmodulated in human malignancies. For instance, the onco-miR-21-5p is known to be upregulated in PDAC and to promote cell proliferation, cell cycle, tumor growth in vivo, and the inhibition of apoptosis in vitro [ 49 ]. The miR-23b-3p directly targets the oncosuppressor PTEN (Phosphatase and TENsin homolog deleted on chromosome 10), its overexpression promotes the tumor growth and liver metastasis of pancreatic cancer xenografts developed in mouse models [ 50 ].…”

“…Furthermore, the onco-miR-27a-3p is upregulated in pancreatic cancer tissue compared to adjacent non-tumor tissues and acts as an oncogene by regulating colony formation, cell proliferation, and migration [ 51 ]. The tumor suppressor miR-24-3p and miR-193a-3p are down-modulated in PDAC, modulating the aggressive properties of PDAC in vitro and in vivo [ 49 ]. Also, miR-34a-5p is down-modulated in pancreatic cancer patients and low miR-34a-5p expression level was reported to correlate with worse prognosis compared to patients with high expressions of the same miRNA in terms of overall survival [ 34 ].…”

Expression of Selected miRNAs in Undifferentiated Carcinoma with Osteoclast-like Giant Cells (UCOGC) of the Pancreas: Comparison with Poorly Differentiated Pancreatic Ductal Adenocarcinoma

“…MiR-21 has been discovered to activate the epidermal growth factor (EGF) pathway by binding to sprouty RTK signaling antagonist 2 (Spry2). This interaction leads to heightened cell proliferation and triggers downstream signaling pathways such as MAPK/ERK and PI3K/Akt [69,70]. Nakamura et al investigated exosomal miRNAs in pancreatic juice, finding that miR-21 and miR-155 can be used to differentiate PDAC patients from CP patients [65].…”

A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment

“…miR-29a and miR-221 are also implicated in PDAC progression, promoting invasion and metastasis [ 43 , 44 , 45 ].…”

“…miR-191 is implicated in the modification of the extracellular matrix and the promotion of distant tumor cell dissemination [42]. miR-29a and miR-221 are also implicated in PDAC progression, promoting invasion and metastasis [43][44][45]. miR-301a-3p and miR-374 also have an oncogenic role in PDAC via inducing migration and increasing the invasiveness of pancreatic cancer cells, with the former targeting SMAD4 expression [46], whereas the latter does so via deregulating Secernin 1 (SRCIN1), leading to its low expression, and to EMT and PDAC progression [47].…”