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      Exosomal microRNA in Pancreatic Cancer Diagnosis, Prognosis, and Treatment: From Bench to Bedside

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          Abstract

          Simple Summary

          Pancreatic cancer is the fourth leading cause of cancer death in the United States and over 90% of the patients suffer from pancreatic ductal adenocarcinoma (PDAC). PDAC is the most lethal gastrointestinal malignancies and only 10% of the people survive more than 5 years, therefore, novel diagnostic, prognostic, and therapeutic strategies are an immediate necessity. Studies have demonstrated microRNAs in bodily fluids that are bound with membranes (exosomes) can act as stable biomarkers both for disease development and metastasis. The diagnostic, prognostic, as well as therapeutic roles of exosomal microRNAs in pancreatic cancer have been discussed in this review.

          Abstract

          Pancreatic cancer is the fourth leading cause of cancer death among men and women in the United States, and pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancer cases. PDAC is one of the most lethal gastrointestinal malignancies with an overall five-year survival rate of ~10%. Developing effective therapeutic strategies against pancreatic cancer is a great challenge. Novel diagnostic, prognostic, and therapeutic strategies are an immediate necessity to increase the survival of pancreatic cancer patients. So far, studies have demonstrated microRNAs (miRNAs) as sensitive biomarkers because of their significant correlation with disease development and metastasis. The miRNAs have been shown to be more stable inside membrane-bound vesicles in the extracellular environment called exosomes. Varieties of miRNAs are released into the body fluids via exosomes depending on the normal physiological or pathological conditions of the body. In this review, we discuss the recent findings on the diagnostic, prognostic, and therapeutic roles of exosomal miRNAs in pancreatic cancer.

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          Most cited references195

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            Shedding light on the cell biology of extracellular vesicles

            Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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              MicroRNAs: target recognition and regulatory functions.

              MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                03 June 2021
                June 2021
                : 13
                : 11
                : 2777
                Affiliations
                Departments of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; uddinh@ 123456wayne.edu (M.H.U.); alhallakm@ 123456karmanos.org (M.N.A.-H.); philipp@ 123456karmanos.org (P.A.P.); mohammad@ 123456karmanos.org (R.M.M.); violan@ 123456karmanos.org (N.V.); wagnerk@ 123456karmanos.org (K.-U.W.)
                Author notes
                [* ]Correspondence: azmia@ 123456karmanos.org ; Tel.: +1-(313)-576-8328
                Author information
                https://orcid.org/0000-0002-0188-6857
                https://orcid.org/0000-0002-6513-3491
                https://orcid.org/0000-0001-8332-5246
                https://orcid.org/0000-0002-5081-0226
                https://orcid.org/0000-0003-1178-9505
                Article
                cancers-13-02777
                10.3390/cancers13112777
                8199777
                34204940
                ecbff90e-9968-484a-8a2b-77136b0e5a49
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 12 April 2021
                : 28 May 2021
                Categories
                Review

                pancreatic cancer,biomarker,exosome,microrna (mirna),early diagnosis,prognosis,treatment

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