RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines

Berardocco, Martina; Radeghieri, Annalisa; Busatto, Sara; Gallorini, M.; Raggi, Chiara; Gissi, Clarissa; D’Agnano, Igea; Bergese, Paolo; Felsani, Armando; Berardi, Anna C.

doi:10.18632/oncotarget.20503

Cited by 34 publications

(35 citation statements)

References 78 publications

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“…IsomiRs with variations at the 3′ end were the predominant isomiR category identified in our data in both stem cell types (Fig. 8 ), and the ratio of isomiR reads to canonical miRNA reads was similar to earlier studies 33 , 73 . Exact function of isomiRs with 3′ modifications are not clearly known but are suggested to be related to a disease state 74 .…”

Section: Discussionsupporting

confidence: 90%

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Small non-coding RNA landscape of extracellular vesicles from human stem cells

Kaur

Abu-Shahba

Paananen

et al. 2018

Sci Rep

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Extracellular vesicles (EVs) are reported to be involved in stem cell maintenance, self-renewal, and differentiation. Due to their bioactive cargoes influencing cell fate and function, interest in EVs in regenerative medicine has rapidly increased. EV-derived small non-coding RNA mimic the functions of the parent stem cells, regulating the maintenance and differentiation of stem cells, controlling the intercellular regulation of gene expression, and eventually affecting the cell fate. In this study, we used RNA sequencing to provide a comprehensive overview of the expression profiles of small non-coding transcripts carried by the EVs derived from human adipose tissue stromal/stem cells (AT-MSCs) and human pluripotent stem cells (hPSCs), both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSC). Both hPSCs and AT-MSCs were characterized and their EVs were extracted using standard protocols. Small non-coding RNA sequencing from EVs showed that hPSCs and AT-MSCs showed distinct profiles, unique for each stem cell source. Interestingly, in hPSCs, most abundant miRNAs were from specific miRNA families regulating pluripotency, reprogramming and differentiation (miR-17-92, mir-200, miR-302/367, miR-371/373, CM19 microRNA cluster). For the AT-MSCs, the highly expressed miRNAs were found to be regulating osteogenesis (let-7/98, miR-10/100, miR-125, miR-196, miR-199, miR-615-3p, mir-22-3p, mir-24-3p, mir-27a-3p, mir-193b-5p, mir-195-3p). Additionally, abundant small nuclear and nucleolar RNA were detected in hPSCs, whereas Y- and tRNA were found in AT-MSCs. Identification of EV-miRNA and non-coding RNA signatures released by these stem cells will provide clues towards understanding their role in intracellular communication, and well as their roles in maintaining the stem cell niche.

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Section: Discussionsupporting

confidence: 90%

“…A low percentage of miRNA reads is typical to extracellular vesicle samples 8 , 28 – 33 . Although the number of miRNA reads per sample was relatively low, miRNA reads were of high quality and mostly close to full length (Supplemental 5), as well as showed robust expression in both sample types (Fig.…”

Section: Discussionmentioning

confidence: 99%

Small non-coding RNA landscape of extracellular vesicles from human stem cells

Kaur

Abu-Shahba

Paananen

et al. 2018

Sci Rep

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“…Proteins were isolated from rBMSCs and from EVs derived from the same rBMSCs using M-PER Mammalian protein extraction reagent supplemented with 1% of Halt Protease, EDTA-free phosphatase-inhibitor cocktail and 1% of EDTA solution (all from Thermo Fisher Scientific), according to the manufacturer's indications [6]. Protein extracts were stored at -20˚C.…”

Section: Protein Preparation From Cells and Evsmentioning

confidence: 99%

“…Recent investigations suggest that the therapeutic efficacy of MSCs depends on paracrine mechanisms and, more recently, their therapeutic potential has been attributed to the secretion of extracellular vesicles (EVs), which are membrane-enclosed lipid vesicles released by cells as mediators of intercellular communication. Ranging in size from *50 nm to > 1μm, EVs carry functional proteins, DNA, mRNA, ncRNA and lipids [5,6].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study

et al. 2020

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Mesenchymal stromal/stem cells (MSCs) are increasingly employed for tissue regeneration, largely mediated through paracrine actions. Currently, extracellular vesicles (EVs) released by MSCs are major mediators of these paracrine effects. We evaluated whether rat-bonemarrow-MSC-derived EVs (rBMSCs-EVs) can ameliorate tendon injury in an in vivo rat model. Pro-collagen1A2 and MMP14 protein are expressed in rBMSC-EVs, and are important factors for extracellular-matrix tendon-remodeling. In addition, we found pro-col-lagen1A2 in rBMSC-EV surface-membranes by dot blot. In vitro on cells isolated from Achilles tendons, utilized as rBMSC-EVs recipient cells, EVs at both low and high doses induce migration of tenocytes; at higher concentration, they induce proliferation and increase expression of Collagen type I in tenocytes. Pretreatment with trypsin abrogate the effect of EVs on cell proliferation and migration, and the expression of collagen I. When either low-or high-dose rBMSCs-EVs were injected into a rat-Achilles tendon injury-model (immediately after damage), at 30 days, rBMSC-EVs were found to have accelerated the remodeling stage of tendon repair in a dose-dependent manner. At histology and histomorphology evaluation, high doses of rBMSCs-EVs produced better restoration of tendon architecture, with optimal tendon-fiber alignment and lower vascularity. Higher EV-concentrations demonstrated greater expression of collagen type I and lower expression of

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“…Gene profiling and protein expression analysis of EVs isolated from metastatic HCC cells identified the mesenchymal-epithelial transition (MET) proto-oncogene S100 family members and caveolins as tumor-promoting molecules in HCC [42,43]. Considerable evidence has indicated that miRNAs contained in EVs contribute to metastasis, chemoresistance, and immunomodulation in different cancer types, including HCC [44]. Min Shi and co-authors have studied the diagnostic and prognostic use of serum EV-miR-638 in HCC patients.…”

Section: Extracellular Vesicles In Hepatocellular Carcinomamentioning

confidence: 99%

Extracellular Vesicles, A Possible Theranostic Platform Strategy for Hepatocellular Carcinoma—An Overview

D’Agnano

Berardi

2020

Cancers

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Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third highest cause of mortality from cancer, largely because of delays in diagnosis. There is currently no effective therapy for advanced stage HCC, although sorafenib, the standard treatment for HCC, systemic therapy (including tyrosine kinase inhibitors and anti-angiogenesis agents), and more recently, immunotherapy, have demonstrated some survival benefit. The measurement and modification of extracellular vesicle (EVs) cargoes—composed of nucleic acids, including miRNAs, proteins, and lipids—holds great promise for future HCC diagnosis, prognosis, and treatment. This review will provide an overview of the most recent findings regarding EVs in HCC, and the possible future use of EVs as “liquid biopsy”-based biomarkers for early diagnosis and as a vehicle for targeted drug-delivery.

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RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines

Abstract: ABSTRACT

Cited by 34 publications

References 78 publications

Small non-coding RNA landscape of extracellular vesicles from human stem cells

Small non-coding RNA landscape of extracellular vesicles from human stem cells

Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study

Extracellular Vesicles, A Possible Theranostic Platform Strategy for Hepatocellular Carcinoma—An Overview

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