Long non‐coding RNAs with low expression levels in cells are enriched in secreted exosomes

Gezer, Uğur; Özgür, Emre; Cetinkaya, Merve; Işin, Mustafa; Dalay, Nejat

doi:10.1002/cbin.10301

Cited by 299 publications

(232 citation statements)

References 24 publications

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“…In esophageal squamous cell carcinoma, TUG1 promoted proliferation and migration in vitro [18]. Gezer et al found that TUG1 were highly enriched in secreted exosomes of HeLa and MCF-7 cells [22]. These data suggested that TUG1 may promote cancer progression.…”

Section: Discussionmentioning

confidence: 98%

Double‐negative feedback loop between long non‐coding RNA TUG1 and miR‐145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

et al. 2015

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a b s t r a c tLncRNAs have a critical role in the regulation of cellular processes such as cancer progression and metastasis. In the present study, we confirmed that TUG1 was overexpressed in bladder cancer tissues and established cell lines. Knockdown of TUG1 inhibited bladder cancer cell metastasis both in vitro and in vivo. Furthermore, we found that TUG1 promoted cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT). Interestingly, TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner. ZEB2 was identified as a down-stream target of miR-145 and TUG1 exerted its function through the miR-145/ZEB2 axis. In summary, our data indicated that blocking TUG1 function may be an effective anti-cancer therapy.

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Section: Discussionmentioning

confidence: 98%

Double‐negative feedback loop between long non‐coding RNA TUG1 and miR‐145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

et al. 2015

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“…One hypothesis suggests that lncRNAs that are stable in human plasma are protected by exosomes (19). It has been demonstrated that exosomes serve an important role in the protection and secretion of non-coding RNAs, including miRNAs and lncRNAs (20,21), and cells affected by stimuli, such as oxidative stress, may increase the secretion of exosomes (22,23). In addition, GC cells are able to release related RNAs into the extracellular environment via exosomes during tumorgenesis (24).…”

Section: Discussionmentioning

confidence: 99%

Plasma lncRNA-GACAT2 is a valuable marker for the screening of gastric cancer

et al. 2016

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Abstract. Long non-coding RNAs (lncRNAs) are crucial in contributing to gastric tumorigenesis and development. However, the diagnostic value of the majority of lncRNAs in gastric cancer (GC) are not clear. The present study investigated the diagnostic value of gastric cancer associated transcript 2 (GACAT2), a lncRNA that is aberrantly expressed in GC tissues. A total of 343 plasma samples from 80 healthy individuals, 29 patients with gastric dysplasia (GD) and 117 paired preoperative and postoperative patients with GC were collected. Plasma GACAT2 levels were subsequently measured by reverse transcription-quantitative polymerase chain reaction. Finally, the associations between plasma GACAT2 levels and various clinicopathological features of patients with GC were assessed. The results demonstrated that plasma GACAT2 levels in preoperative patients with GC were significantly higher than those in the postoperative group (P=0.031). Compared with healthy individuals, plasma GACAT2 levels were significantly increased in patients with GD (P<0.001) and preoperative patients with GC (P=0.040). Moreover, the individual relative changes of plasma GACAT2 expression following surgery were significantly associated with lymphatic metastasis (P=0.034), distal metastasis (P=0.035) and perineural invasion (P=0.039). Therefore, the results of the current study suggest that plasma-based GACAT2 may be developed as a tumor marker to screen and predict the prognosis of GC patients. IntroductionGastric cancer (GC) is one of the most prevalent malignant tumors (1). A number of cancer prevention studies have demonstrated that the most effective way to reduce GC-associated mortality is through early diagnosis and appropriate treatment (2-4). However, the diagnosis rate of early GC remains extremely low (<10%) (5). Patients with GC are usually diagnosed following identification of tumors on B-mode ultrasound, computerized tomography, or magnetic resonance imaging scans. However, early GC tumors are often not large enough to be detected by conventional imaging techniques. Furthermore, the sensitivity and specificity of traditional tumor markers are not satisfactory (6). Thus, investigations into new, more efficient tumor markers are important to improve early diagnosis of this disease.Long non-coding RNAs (lncRNAs) are a class of regulatory non-coding RNAs (7). Previous studies have investigated the roles of lncRNAs in tumorigenesis and cancer development. For example, Zang et al (8) reported that lncRNA-PEG10 expression was upregulated in esophageal cancer tissues, and that it regulated the proliferation and invasion of cancer cells. Furthermore, Shao et al (9) demonstrated that lncRNA-AA174084 expression was downregulated in gastric cancer tissues. A previous study determined that gastric cancer associated transcript 2 (GACAT2) was not only significantly downregulated in gastric cancer tissue, but was also aberrantly expressed in gastric precancerous lesions and gastric cell lines (10).Blood is one of the most commonly used samples in ...

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“…16) A recent study showed that ncRNAs were highly abundant in exosomes secreted by HeLa and MCF-7 cell lines. 29) More recently, ncRNAs of human urinary exosomes were analyzed using NGS. 20) Thus, these results show that exosomes can entrap many types of RNAs and potentially transfer large amounts of information between cells.…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing of Protein-Coding and Long Non-protein-Coding RNAs in Two Types of Exosomes Derived from Human Whole Saliva

Ogawa

Tsujimoto

Yanoshita

2016

Biological & Pharmaceutical Bulletin

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Exosomes are small extracellular vesicles containing microRNAs and mRNAs that are produced by various types of cells. We previously used ultrafiltration and size-exclusion chromatography to isolate two types of human salivary exosomes (exosomes I, II) that are different in size and proteomes. We showed that salivary exosomes contain large repertoires of small RNAs. However, precise information regarding long RNAs in salivary exosomes has not been fully determined. In this study, we investigated the compositions of protein-coding RNAs (pcRNAs) and long non-protein-coding RNAs (lncRNAs) of exosome I, exosome II and whole saliva (WS) by next-generation sequencing technology. Although 11% of all RNAs were commonly detected among the three samples, the compositions of reads mapping to known RNAs were similar. The most abundant pcRNA is ribosomal RNA protein, and pcRNAs of some salivary proteins such as S100 calcium-binding protein A8 (protein S100-A8) were present in salivary exosomes. Interestingly, lncRNAs of pseudogenes (presumably, processed pseudogenes) were abundant in exosome I, exosome II and WS. Translationally controlled tumor protein gene, which plays an important role in cell proliferation, cell death and immune responses, was highly expressed as pcRNA and pseudogenes in salivary exosomes. Our results show that salivary exosomes contain various types of RNAs such as pseudogenes and small RNAs, and may mediate intercellular communication by transferring these RNAs to target cells as gene expression regulators.Key words exosome; transcriptome; human whole saliva; next-generation sequencing; non-coding RNA; pseudogene Human whole saliva (WS) contains an aqueous complex mixture of proteins, peptides, hormones, metabolites, DNAs and RNAs. WS contributes to maintain the integrity of the oral cavity through its lubricating, antibacterial, antiviral and buffering actions, and facilitates chewing and swallowing food. It plays an important role in front-line body defense. Because WS can be collected simply, cheaply and noninvasively, it has been used to monitor human health and disease. Because saliva contains ribonucleases and nucleases from various sources, which influence RNA stability, relatively few studies have analyzed human salivary RNA.1) Salivary nucleotides are protected from degradation by inclusion in extracellular vesicles such as exosomes. Recently, RNAs and DNAs in WS have been highlighted in the fields of biomarker research, disease diagnostics and forensic study. 2-4)Exosomes are small (30-100 nm) membrane vesicles of endocytic origin that are released into the extracellular environment upon fusion of multivesicular bodies with the plasma membrane. Exosomes are present in various body fluids including blood, breast milk, malignant ascites, urine, amniotic fluid and saliva. 5) Exosomes can contain the proteins and nucleic acids of their cell of origin and can transfer their contents to recipient cells at a distance. 5) Exosomes are now thought to be secreted by various cell types, and numerous comp...

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Long non‐coding RNAs with low expression levels in cells are enriched in secreted exosomes

Cited by 299 publications

References 24 publications

Double‐negative feedback loop between long non‐coding RNA TUG1 and miR‐145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

Double‐negative feedback loop between long non‐coding RNA TUG1 and miR‐145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

Plasma lncRNA-GACAT2 is a valuable marker for the screening of gastric cancer

Next-Generation Sequencing of Protein-Coding and Long Non-protein-Coding RNAs in Two Types of Exosomes Derived from Human Whole Saliva

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