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      Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance

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          Abstract

          Exosomes are nanoscale extracellular vesicles secreted by a variety of cells, affecting the physiological and pathological homeostasis. They carry various cargoes including proteins, lipids, DNA, and RNA and have emerged as critical mediators of intercellular communication. During cell–cell communication, they can internalize either by autologous or heterologous recipient cells, which activate different signaling pathways, facilitating malignant progression of cancer. Among different types of cargoes in exosomes, the endogenous non-coding RNAs, such as circular RNAs (or circRNAs), have gained tremendous attention for their high stability and concentration, playing promising functional roles in cancer chemotherapeutic response by regulating the targeted gene expression. In this review, we primarily described the emerging evidence demonstrating the important roles of circular RNAs derived from exosomes in the regulation of cancer-associated signaling pathways that were involved in cancer research and therapeutic interventions. Additionally, the relevant profiles of exosomal circRNAs and their biological implications have been discussed, which is under investigation for their potential effect on the control of cancer therapeutic resistance.

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          Most cited references93

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          Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

          Cancer immunotherapy can induce long lasting responses in patients with metastatic cancers of a wide range of histologies. Broadening the clinical applicability of these treatments requires an improved understanding of the mechanisms limiting cancer immunotherapy. The interactions between the immune system and cancer cells are continuous, dynamic, and evolving from the initial establishment of a cancer cell to the development of metastatic disease, which is dependent on immune evasion. As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
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            Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis.

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              Circular intronic long noncoding RNAs.

              We describe the identification and characterization of circular intronic long noncoding RNAs in human cells, which accumulate owing to a failure in debranching. The formation of such circular intronic RNAs (ciRNAs) can be recapitulated using expression vectors, and their processing depends on a consensus motif containing a 7 nt GU-rich element near the 5' splice site and an 11 nt C-rich element close to the branchpoint site. In addition, we show that ciRNAs are abundant in the nucleus and have little enrichment for microRNA target sites. Importantly, knockdown of ciRNAs led to the reduced expression of their parent genes. One abundant such RNA, ci-ankrd52, largely accumulates to its sites of transcription, associates with elongation Pol II machinery, and acts as a positive regulator of Pol II transcription. This study thus suggests a cis-regulatory role of noncoding intronic transcripts on their parent coding genes. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                15 February 2023
                2023
                : 14
                : 1093175
                Affiliations
                [1] 1 Department of Pathology , Xiangya Changde Hospital , Changde, Hunan, China
                [2] 2 Department of Pharmacy , Xiangya Hospital , Central South University , Changsha, Hunan, China
                [3] 3 National Clinical Research Center for Geriatric Disorders , Xiangya Hospital , Central South University , Changsha, Hunan, China
                [4] 4 Department of Pathology , Xiangya Hospital , Central South University , Changsha, Hunan, China
                [5] 5 Pritzker School of Molecular Engineering , Ben May Department for Cancer Research , University of Chicago , Chicago, IL, United States
                Author notes

                Edited by: Christian Celia, University of Studies G. d’Annunzio Chieti and Pescara, Italy

                Reviewed by: Jinhui Liu, Nanjing Medical University, China

                Yiqun Jiang, Hunan Normal University, China

                *Correspondence: Wei Zhu, zhuwei861204@ 123456csu.edu.cn
                [ † ]

                These authors have contributed equally to this work

                This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology

                Article
                1093175
                10.3389/fphar.2023.1093175
                9974836
                36874026
                a068596d-7c16-48b7-b781-bc5453306706
                Copyright © 2023 Kang, Yan, Liu, Liang, Xu, Zhu and Thakur.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 November 2022
                : 30 January 2023
                Funding
                This study is supported by grants from the National Natural Science Foundation of China (82272659), the Science and Technology Innovation Program of Hunan Province (2022RC1210), and the horizontal project (2022, 1 43010100; 2021-021, 143010100).
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                exosomes,extracellular vesicles,cancer,circular rnas,drug resistance

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