Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma

He, Shan; Li, Ziming; Ye, Yu; Zeng, Qingyu; Cheng, Yirui; Ji, Wei; Xia, Weiliang; Lü, Shun

doi:10.1016/j.yexcr.2019.03.035

Cited by 91 publications

(75 citation statements)

References 39 publications

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“…In addition, miR-499a contributes to the migration and proliferation of hepatitis B virus-associated hepatocellular carcinoma (HCC) cells (45). Recently, miR-499a-5p has been observed to promote migration, proliferation and epithelial-to-mesenchymal transition in metastatic lung cancer cell lines, via modulation of the mTOR pathway (46); however, the functions of miR-499 in cervical cancer development have not yet been fully elucidated. In the present study, miR-299a expression was upregulated in cervical cancer samples and was revealed to downregulate CYP26B1 expression.…”

Section: Discussionmentioning

confidence: 99%

ADH7, miR‑3065 and LINC01133 are associated with cervical cancer progression in different age groups

et al. 2020

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The aim of the present study was to identify potential therapeutic targets that serve crucial roles in the progression of cervical cancer. Clinical data, RNA sequencing (RNAseq)-counts and micro (mi)RNA data regarding cervical squamous cell carcinoma were retrieved from The Cancer Genome Atlas, and analyses were performed using the University of California Santa Cruz database. RNAseq and miRNA data were stratified into 3 groups (according to the patients' age), and genes were re-annotated and preprocessed prior to Mfuzz time clustering analysis. Subsequently, enrichment analyses were performed in order to identify differentially expressed mRNAs (DEmRNAs) and a protein-protein interaction analysis network was constructed. miRNA-gene, miRNA-lncRNA, and long non-coding (lnc)RNA-mRNA pairs were collected and the lncRNA-miRNA-mRNA competing endogenous (ce)RNA network was established. Further enrichment analyses were performed in order to identify crucial mRNAs in the ceRNA network. Finally, survival and drug association analyses were implemented. A total of 269 DEmRNAs [including alcohol dehydrogenase 7 (ADH7), vestigial-like family member 3 (VGLL3) and cytochrome P450, family 26, subfamily B, polypeptide 1 (CYP26B1)], 274 DElncRNAs (including LINC01133) and 16 DEmiRNAs (including miR-3065 and miR-330) were identified. There were 102 lncRNAs, 15 miRNAs, 15 mRNAs and 522 interaction pairs in the ceRNA network. In particular, ADH7 was regulated by miR-3065, and miR-3065 interacted with LINC01133 in the ceRNA network. Furthermore, ADH7 and CYP26B1 were enriched in the retinoic acid metabolic process and the retinol metabolism pathway. ADH7 and VGLL3 were significantly associated with the cervical cancer survival rate. ADH7, VGLL3, CYP26B1, miR-3065, miR-330, miR-499a and LINC01133 play pivotal roles in the progression of cervical cancer in different age groups.

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Section: Discussionmentioning

confidence: 99%

ADH7, miR‑3065 and LINC01133 are associated with cervical cancer progression in different age groups

et al. 2020

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“…They contain many biologically active substances secreted by recipient cells, such as noncording RNA (ncRNA), proteins, and mRNA. And it plays an important role in the extracellular microenvironment and intercellular communication [12,[15][16][17][18]. Kato [19] extracted exosomes from the supernatant of IL-1β-induced synovial fibroblasts and then added exosomes to chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

“…This suggests that synovial tissue may regulate chondrocytes by secreting exosomes. Number of articles [15][16][17][18][19][20][21][22] has conducted detailed studies on how to extract cell supernatants and exosomes in body fluids, but few of articles had studied the extraction and identification of exosomes in tissues. To the best of our knowledge, any article has been published on how to extract and identify exosomes from synovial tissue.…”

Section: Introductionmentioning

confidence: 99%

Extraction and identification of synovial tissue-derived exosomes by different separation techniques

et al. 2020

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Objective: The aim of this study is to compare the efficiency of different separation techniques for extracting synovial tissue-derived exosomes. Methods: The synovial tissue discarded during knee arthroscopy or total knee arthroplasty surgery was collected from the Third Affiliated Hospital of Beijing University of Chinese Medicine. Ultracentrifugation (UC), filtration combined with size exclusion chromatography (SECF), and 8% polyethylene glycol (PEG) were used to extract synovial tissue-derived exosomes. Transmission electron microscopy (TEM), nanoparticle tracer analysis (NTA), and Western Blot (WB) were used to detect the morphology, particle size, and biomarker proteins (CD9, CD63, Flotillin-1, and calnexin) of exosomes. Results: The extracts of enriched round and discoid vesicles were successfully extracted with UC, SECF, and PEG. The results of TEM have shown that all three extraction methods can extract circular or elliptical vesicles with discand cup-shaped structures from the synovial tissue, with the diameter is about 30-150 nm. NTA suggested the main peaks of three groups of exosomes are around 100-120 nm, and the concentration of the three groups of exosomes was greater than 1 × 10 10 /ml. The results of WB showed that three positive protein markers (CD9, CD63, and Flotillin-1) were highly expressed in the suspension extracted by the three methods and low in the synovial tissue. However, the negative protein (calnexin) was highly expressed in synovial tissues and PEG group, while low in UC and SECF group. Conclusion: Morphology, particle size, and labeled protein marker detection confirmed that UC, SECF, and PEG can extract exosomes derived from synovial tissue; UC and SECF are more recommended for the extraction of synovial tissue-derived exosomes, which provides a methodological basis for studying the function and mechanism of synovial tissue exosomes in the future.

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“…16 MiR-499a-5p has gained increasing attention in cancer research because of its anti-tumor action. The aberrant downregulation of miR-499a-5p expression has been identified in oral squamous cell carcinoma, 17 osteosarcoma, 12 and lung adenocarcinoma; 13 however, little is known regarding its expression in CC. Here, in this study, we firstly determined the expression level of miR-499a-5p in CC tissues and cell lines by qRT-PCR and found that miR-499a-5p was significantly downregulated in CC tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

“…12 Additionally, it has been reported that miR-499a-5p promoted lung cancer cell proliferation, migration, and epithelial-mesenchymal transition (EMT) in vitro and enhanced tumor growth in vivo. 13 However, the expression of miR-499a-5p in CC tissues remains unclear, and whether it modulated the radiosensitivity of CC cells is still unknown. Additionally, the interrelation of miR-499a-5p and eIF4E in CC development was also not completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

<p>MiR-499a-5p Inhibits Pr5/4/20 publish l Cancer Cells via Targeting eIF4E</p>

Gu¹,

Ma²,

Liu³

et al. 2020

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Introduction: The present study aimed to explore the role of miR-499a-5p and its molecular mechanism in cervical cancer (CC). Methods: Quantitative real-time PCR (QRT-PCR) and Western blotting were performed to detect the expression of miR-499a-5p and eukaryotic translation initiation factor 4E (eIF4E) in CC tissues and cell lines. The proliferation, migration, and invasion of CC cells were detected by MTT assay, wound healing assay, and Transwell assay. Apoptosis was evaluated by flow cytometry and alterations of apoptosis-related genes. The effect of miR-499a-5p on epithelial-mesenchymal transition (EMT) was examined by determining the protein levels of EMT-associated genes. Then, colony formation assay was used to determine the radiosensitivity of CC cells. A dualluciferase reporter assay was performed to confirm the direct target of miR-499a-5p. Results: MiR-499a-5p was significantly downregulated in CC tissues and cell lines. Overexpression of miR-499a-5p or eIF4E knockdown markedly inhibited cell proliferation, invasion, migration, and EMT, and enhanced apoptosis. eIF4E was predicted and verified as a target gene of miR-499a-5p. The influence of miR-499a-5p upregulation on proliferation, apoptosis, invasion, migration, EMT, and radiosensitivity was abrogated by eIF4E overexpression. Discussion: MiR-499a-5p promoted the apoptosis and radiosensitivity and inhibited proliferation, invasion, migration, and EMT by directly targeting eIF4E in CC cells.

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Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma

Cited by 91 publications

References 39 publications

ADH7, miR‑3065 and LINC01133 are associated with cervical cancer progression in different age groups

ADH7, miR‑3065 and LINC01133 are associated with cervical cancer progression in different age groups

Extraction and identification of synovial tissue-derived exosomes by different separation techniques

<p>MiR-499a-5p Inhibits Pr5/4/20 publish l Cancer Cells via Targeting eIF4E</p>

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