MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway

Lou, Guohua; Chen, Liang; Xia, Caixia; Wang, Weina; Qi, Jinjin; Li, Aichun; Zhao, Liying; Chen, Zhi; Zheng, Min; Liu, Yanning

doi:10.1186/s13046-019-1512-5

Cited by 211 publications

(150 citation statements)

References 35 publications

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“…Exosomes-delivered UCA1 led to enhanced tamoxifen resistance in breast cancer 15 . Recently, MSCs-derived exosomes have gradually attracted our attention 16,17 . Especially, exosomes could transmit lncRNAs to cancer cells and therefore accelerate the progression of multiple cancers 18,19 .…”

Section: Introductionmentioning

confidence: 99%

Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway

Wang

et al. 2020

Cell Death Dis

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Increasing evidence indicates that long non-coding RNAs (lncRNAs) are associated with the progression of human cancers. However, the expression level and function of LINC01559 (long intergenic non-protein coding RNA 1559) in gastric cancer (GC) are rarely reported. Here we found that LINC01559 was upregulated in GC tissues based on GEPIA (Gene Expression Profiling Interactive Analysis) and TCGA (The Cancer Genome Atlas) databases. Also, LINC01559 was expressed at a lower level in GC cells than in mesenchymal stem cells (MSCs). In vitro experiments revealed that silencing LINC01559 remarkably hindered GC cell proliferation, migration and stemness. Then, we identified that LINC01559 was transmitted form MSCs to GC cells via the exosomes. Immunofluorescence staining and electron microscope validated the existence of exosomes in GC cells. Mechanistically, LINC01559 sponged miR-1343-3p to upregulate PGK1 (phosphoglycerate kinase 1), therefore activating PI3K/AKT pathway. Moreover, LINC01559 recruited EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to PTEN (phosphatase and tensin homolog) promoter, inducing the methylation of PTEN promoter and finally resulting in PTEN repression. Of note, LINC01559 targeted both PGK1 and PTEN to promote GC progression by activating PI3K/AKT pathway. Taken together, our study demonstrated that LINC01559 accelerated GC progression via upregulating PGK1 and downregulating PTEN to trigger phosphatidylinositol 3-kinase/AKT serine/threonine kinase (PI3K/AKT) pathway, indicating LINC01559 as a potential biomarker for GC treatment.

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Section: Introductionmentioning

confidence: 99%

Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway

Wang

et al. 2020

Cell Death Dis

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“…Furthermore, treatment with these exosomes altered the mTOR pathway and decreased chemoresistance in these cells. They observed similar effects in-vivo, confirming the utility of engaging exosomes as therapeutic vehicles [104]. A separate study utilizing a rat model of HCC also demonstrated the benefit of exploiting MSCs-AdExos as therapeutic vehicles.…”

Section: Exosomes As Therapeutic Vehiclesmentioning

confidence: 66%

“…For example, miRNA-122 has been demonstrated to promote chemosensitivity in HCC, and treatment with miRNA-122-enriched exosomes altered gene expression in recipient HCC and increased chemotherapeutic drug sorafenib sensitivity both in vitro and in vivo [103]. Another group utilized MSCs-AdExos to package miRNA-199a-3p, which has been shown to reduce HCC cell aggressiveness and enhance chemosensitivity to doxorubicin [104]. Furthermore, treatment with these exosomes altered the mTOR pathway and decreased chemoresistance in these cells.…”

Section: Exosomes As Therapeutic Vehiclesmentioning

confidence: 99%

The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells

Ríos-Colón

Arthur

Niture

et al. 2020

Cells

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Exosomes are membrane-bound extracellular vesicles (EVs) that transport bioactive materials between cells and organs. The cargo delivered by exosomes can alter a wide range of cellular responses in recipient cells and play an important pathophysiological role in human cancers. In hepatocellular carcinoma (HCC), for example, adipocyte- and tumor-secreted factors contained in exosomes contribute to the creation of a chronic inflammatory state, which contributes to disease progression. The exosome-mediated crosstalk between adipocytes and liver cancer cells is a key aspect of a dynamic tumor microenvironment. In this review, we summarize the role of increased adiposity and the role of adipocyte-derived exosomes (AdExos) and HCC-derived exosomes (HCCExos) in the modulation of HCC progression. We also discuss recent advances regarding how malignant cells interact with the surrounding adipose tissue and employ exosomes to promote a more aggressive phenotype.

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“…Quite in line with our study, a recent study noted that miR-199a-modified adMSC-Exos improved the chemosensitivity of hepatocellular carcinoma cells through the mTOR pathway. 29 We therefore explored the potential molecules involved in the adMSC-Exos-mediated DDP sensitivity in BC cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Adipose Mesenchymal Stem Cell-Derived Exosomal microRNA-1236 Reduces Resistance of Breast Cancer Cells to Cisplatin by Suppressing SLC9A1 and the Wnt/β-Catenin Signaling</p>

Jia¹,

Zhu²,

Sun³

et al. 2020

CMAR

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Background: Emerging evidence has noted the versatile functions of mesenchymal stem cell-derived exosomes (MSC-Exos) in cancer control. This work aims to probe to function of adipose MSC-Exos (adMSC-Exos) in drug-resistance of breast cancer (BC) cells to cisplatin (DDP) and the molecules involved. Methods: Parental and DDP-resistant BC cell lines MCF-7 and MDA-MB-231 were used. All cells were pre-treated with adMSC-Exos. Then, the viability and apoptosis of cells after DDP treatment were determined. Differentially expressed miRNAs after adMSC-exo treatment were screened out. Rescue experiments were conducted by pre-transfecting miR-1236 inhibitor into adMSCs, and the role of miR-1236 in DDP sensitivity was determined. Targeting mRNAs of miR-1236 were predicted by bioinformatics analysis. Altered SLC9A1 expression was administrated to evaluate its function in DDP resistance. Results: The adMSC-Exos notably increased the sensitivity of either parental or DDPresistant BC cells to DDP. SLC9A1 was notably highly expressed in DDP-resistant cells but inhibited following adMSC-exo administration. Importantly, miR-1236, which could directly bind to SLC9A1 and suppress its expression, was confirmed as an enriched miRNA in adMSC-Exos. Either inhibition of miR-1236 or upregulation of SLC9A1 blocked the pro-sensitize roles of adMSC-Exos. In addition, the Wnt/β-catenin pathway activity was suppressed by adMSC-Exos but recovered by SLC9A1. Conclusion: This study evidenced that adMSC-Exos carry miR-1236 to increase sensitivity of BC cells to DDP with the involvement of SLC9A1 downregulation and Wnt/β-catenin inactivation. This finding may offer novel insights into treatment for drug-resistant BC.

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MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway

Cited by 211 publications

References 35 publications

Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway

Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway

The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells

<p>Adipose Mesenchymal Stem Cell-Derived Exosomal microRNA-1236 Reduces Resistance of Breast Cancer Cells to Cisplatin by Suppressing SLC9A1 and the Wnt/β-Catenin Signaling</p>

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