The decade of exosomal long RNA species: an emerging cancer antagonist

Zhou, Ruihao; Chen, Kaddie Kwok; Zhang, Jingtao; Xiao, Bufan; Huang, Zhaofeng; Cheng, Ju; Sun, Jun; Zhang, Feifei; Lv, Xiao; Huang, Guofu

doi:10.1186/s12943-018-0823-z

Cited by 132 publications

(115 citation statements)

References 137 publications

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“…Our data verify that RNAs are able to be physically transmitted from a somatic tissue, in this case the brain, to the germline and to offspring in male mice. The mode of transport for the RNA via the lymph and bloodstream is likely to be vesicles, which would provide a secure environment to avoid degradation and increase stability [29,30]. Although we could only find one case where our detection system captured the RNA in the vesicle-containing fractions of ultracentrifuged whole blood ( Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

O’Brien

Ensbey

Day

et al. 2019

Preprint

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AbstractBackgroundThe traditional concept that heritability occurs exclusively from the transfer of germline-restricted genetics is being challenged by the increasing accumulation of evidence confirming the existence of experience-dependent transgenerational inheritance. However, questions remain unanswered as to how heritable information can be passed from somatic cells. Previous studies have implicated the critical involvement of RNA in heritable transgenerational effects and the high degree of mobility and genomic impact of RNAs in all organisms is an attractive model for the efficient transfer of genetic information.ResultsWe hypothesized that RNA may be transported from a somatic tissue, in this case the brain, of an adult male mouse to the germline, and subsequently to offspring. To investigate this, we injected one hemisphere of the male mouse striatum with an AAV1/9 virus expressing human pre-MIR941 (MIR941). After 2, 8 and 16 weeks following injection, we used an LNA-based qPCR system to detect the presence of virus and human MIR941 in brain, peripheral tissues and offspring, from injected male mice mated with uninjected females. Virus was never detected outside of the brain. Verification of single bands of the correct size for MIR941 was performed using Sanger sequencing while quantitation demonstrated that a small percentage (∼ 1-8%) of MIR941 is transported to the germline and to offspring in about a third of the cases.ConclusionsWe show that somatic RNA can be transported to the germline and passed on to offspring, thereby providing additional evidence of a role for RNA in somatic cell-derived transgenerational effects.

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Section: Discussionmentioning

confidence: 99%

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

O’Brien

Ensbey

Day

et al. 2019

Preprint

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“…Long non-coding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that have limited or no proteincoding capacity [17]. Exosome-derived lncRNAs have been detected in a wide range of bodily fluids due to active cellular secretion [18].…”

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confidence: 99%

Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway

Xiao

Liu

et al. 2020

J Exp Clin Cancer Res

112

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Background: Exosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells. Human metastases-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA known to promote cell proliferation, metastasis, and invasion in colorectal cancer (CRC).Methods: The expression of MALAT1 was analyzed in CRC using qRT-PCR. FUT4 and fucosylation levels were detected in CRC clinical samples and CRC cell lines by immunofluorescent staining, western blot and lectin blot analysis. CRC derived exosomes were isolated and used to examine their tumor-promoting effects in vitro and in vivo. Results:The invasive and metastatic abilities of primary CRC cells were enhanced after exposure to exosomes derived from highly metastatic CRC cells, which increased the fucosyltransferase 4 (FUT4) levels and fucosylation not by directly transmitting FUT4 mRNA. Exosomal MALAT1 increased FUT4 expresssion via sponging miR-26a/26b. Furthermore, MALAT1/miR-26a/26b/FUT4 axis played an important role in exosome-mediated CRC progression. Exosomal MALAT1 also mediated FUT4-associated fucosylation and activated the PI3K/AKT/mTOR pathway.Conclusions: These data indicated that exosomal MALAT1 promoted the malignant behavior of CRC cells by sponging miR-26a/26b via regulating FUT4 and activating PI3K/Akt/mTOR pathway.Keywords: CRC, Exosomal MALAT1, FUT4, miR-26a/26b, PI3K/Akt/mTOR pathway Background Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality [1,2]. More than 60% of CRC patients have initiated the metastatic process by the time of diagnosis [3]. Although there are multiple tests available for CRC screening, each method has its own limitations in terms of sensitivity and specificity. To the best of our knowledge, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are well established tumor markers with low sensitivity and specificity for early detection of CRC [4]. Hence, ideal CRC-specific biomarkers are urgently required to improve the current CRC diagnostic strategies.Exosomes, membrane vesicles of endocytic origin ranging in size from 30 to 150 nm approximately, are emerging as key players in intercellular communication between cancer cells and their microenvironment [5]. A distinct feature of exosomes is that they efficiently carry and deliver molecular signatures (proteins, lipids, RNA

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“…Additionally, Rab27a supports exosome could modify the tumour microenvironment via advancing recruitment and differentiation of bone marrow‐derived neutrophils to cancer cells . Furthermore, a few studies suggest that tumour‐derived EVs facilitate cancer progression by attenuating immune and more specific EVs could diminish the cytotoxicity of natural killer cells and T cell in immunoreaction . Tumour‐derived EVs also could influence the cancer cells themselves via autocrine to irritate the invasion and migration, and reduce adhesion abilities as well via enhancing MMP‐9 or chemokine receptor type 4 (CXCR4) …”

Section: Modulation Of the Tumour Microenvironmentmentioning

confidence: 99%

Extracellular vesicles in urologic malignancies—Implementations for future cancer care

Zhang

Xia

et al. 2019

Cell Proliferation

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Extracellular vesicles (EVs), a heterogeneous group of vesicles differing in size and shape, cargo content and function, are membrane‐bound and nano‐sized vesicles that could be released by nearly all variations of cells. EVs have gained considerable attention in the past decades for their functions in modulating intercellular signalling and roles as potential pools for the novel diagnostic and prognostic biomarkers, as well as therapeutic targets in several cancers including urological neoplasms. In general, human and animal cells both can release distinct types of EVs, including exosomes, microvesicles, oncosomes and large oncosomes, and apoptotic bodies, while the content of EVs can be divided into proteins, lipids and nucleic acids. However, the lack of standard methods for isolation and detection platforms rein the widespread usage in clinical applications warranted furthermore investigations in the development of reliable, specific and sensitive isolation techniques. Whether and how the EVs work has become pertinent issues. With the aid of high‐throughput proteomics or genomics methods, a fully understanding of contents contained in EVs from urogenital tumours, beyond all doubt, will improve our ability to identify the complex genomic alterations in the process of cancer and, in turn, contribute to detect potential therapeutic target and then provide personalization strategy for patient.

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The decade of exosomal long RNA species: an emerging cancer antagonist

Cited by 132 publications

References 137 publications

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway

Extracellular vesicles in urologic malignancies—Implementations for future cancer care

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