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      Exosome-transmitted long non-coding RNA SENP3-EIF4A1 suppresses the progression of hepatocellular carcinoma

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          Abstract

          Extracellular communication mediated by exosomes in a tumor microenvironment can substantially affect tumor progression. However, the effect of exosomal long non-coding RNA SENP3-EIF4A1 on hepatocellular carcinoma (HCC) is still unclear. In this study, SENP3-EIF4A1 expressions in patients with HCC and healthy controls were detected and compared. Results showed that SENP3-EIF4A1 was significantly reduced in HCC tissues and exosomes from the plasma of patients with HCC ( P<0.05) and was primarily encapsulated by exosomes. The patients with HCC and the healthy controls could be distinguished using exosomal SENP3-EIF4A1 (AUC=0.8028). The transfer of exosomal SENP3-EIF4A1 secreted by normal cells to HCC cells stimulated apoptosis and weakened the invasion and migration abilities of HCC cells to suppress their malignant biological behavior ( P<0.05). Additionally, exosomal SENP3-EIF4A1 was capable of inhibiting tumor growth in vivo and modulating the expression of ZFP36 by competitively binding to miR-9-5p. In conclusion, exosomal SENP3-EIF4A1 is a new favorable biomarker for clinically detecting HCC, and SENP3-EIF4A1 can be transmitted by exosomes from normal cells to HCC cells to inhibit the in vitro and in vivo development of HCC. Thus, exosomal SENP3-EIF4A1 is involved in the communication between normal cells and HCC cells during the onset of HCC.

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          History, Discovery, and Classification of lncRNAs.

          The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of eukaryotic transcriptomes.
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            Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer

            Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients. In pilot study, our results indicated that exosomal CRNDE-h was detectable and stable in serum of CRC patients, and derived from tumor cells. Then, the increased expression of exosomal CRNDE-h was successfully validated in 148 CRC patients when compared with colorectal benign disease patients and healthy donors. Exosomal CRNDE-h level significantly correlated with CRC regional lymph node metastasis (P = 0.019) and distant metastasis (P = 0.003). Moreover, at the cut-off value of 0.020 exosomal CRNDE-h level of serum, the area under ROC curve distinguishing CRC from colorectal benign disease patients and healthy donors was 0.892, with 70.3% sensitivity and 94.4% specificity, which was superior to carcinoembryogenic antigen. In addition, high exosomal CRNDE-h level has a lower overall survival rates than that for low groups (34.6% vs. 68.2%, P < 0.001). In conclusion, detection of lncRNA CRNDE-h in exosome shed a light on utilizing exosomal CRNDE-h as a noninvasive serum-based tumor marker for diagnosis and prognosis of CRC.
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              Exosome–transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression

              Background Extracellular communication within the tumor microenvironment plays a critical role in tumor progression. Although exosomes can package into long non-coding RNAs (lncRNAs) to mediate extracellular communication, the role of exosomal lncRNA PTENP1 in bladder cancer (BC) remains unclear. Method We detected PTENP1 expression between patients with BC and healthy controls; the expression occurred in tissues and exosomes from plasma. We assessed the diagnostic accuracy by the receiver operating characteristic curve (ROC) and the area under curve (AUC). Cell phenotypes and animal experiments were performed to determine the effect of exosomal PTENP1. Results PTENP1 was significantly reduced in BC tissues and in exosomes from plasma of patients with BC (P < 0.05). We found that PTENP1 was mainly wrapped by exosomes. Exosomal PTENP1 could distinguish patients with BC from healthy controls (AUC = 0.743; 95% confidence interval (CI) = 0.645–0.840). Normal cells secreted exosomal PTENP1 and transmitted it to BC cells, thus inhibiting the biological malignant behavior of BC cells by increasing cell apoptosis and reducing the ability to invade and migrate (P < 0.05). Exosomal PTENP1 could suppress tumor growth in vivo. Furthermore, exosomal PTENP1 mediated the expression of PTEN by competitively binding to microRNA-17. Conclusion Exosomal PTENP1 is a promising novel biomarker that can be used for the clinical detection of BC. Exosomes derived from normal cells transfer PTENP1 to BC cells, which reduce the progression of BC both in vitro and in vivo and suggest that exosomal PTENP1 participates in normal-cell-to-bladder-cell communication during the carcinogenesis of BC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0880-3) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                30 June 2020
                27 June 2020
                : 12
                : 12
                : 11550-11567
                Affiliations
                [1 ]Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China
                [2 ]Clinic Medicine Research Center of Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China
                [3 ]Library of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China
                [4 ]Department of Infectious Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China
                [5 ]Centre for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Yibin Deng; email: dengyb75@163.com
                Article
                103302 103302
                10.18632/aging.103302
                7343467
                32602848
                bf5ac74e-191c-4675-83ec-fdde32b5d196
                Copyright © 2020 Wang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 September 2019
                : 27 April 2020
                Categories
                Research Paper

                Cell biology
                hepatocellular carcinoma,senp3-eif4a1,exosomes,biomarker,cerna
                Cell biology
                hepatocellular carcinoma, senp3-eif4a1, exosomes, biomarker, cerna

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