Extracellular vesicle‐mediated transfer of long non‐coding RNA ROR modulates chemosensitivity in human hepatocellular cancer

Takahashi, Kenji; Yan, Irene K.; Kogure, Takayuki; Haga, Hiroaki; Patel, Tushar

doi:10.1016/j.fob.2014.04.007

Cited by 383 publications

(307 citation statements)

References 31 publications

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“…16 More importantly, exosomes-shuttling miRNAs probably conferred this resistance delivery. Followed by these studies, more and more evidence confirmed this observation in other cancers including breast cancer, prostate cancer, hepatocellular cancer, [17][18][19][20] and so on. However, similar to our previous study, most of these literatures mainly reported this phenomenon and few researchers 13 conduct in-depth study and systematically explore its detailed mechanism.…”

Section: Introductionmentioning

confidence: 65%

Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

Qin

Zhou

et al. 2017

IJN

211

163

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Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

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Section: Introductionmentioning

confidence: 65%

Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

Qin

Zhou

et al. 2017

IJN

211

163

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“…Exosomes contain a complex mixture of miRs, mRNAs, and proteins, and their ability to traverse the intercellular space and to be taken up by neighboring cells is becoming increasingly recognized as an important mechanism for delivering genetic, epigenetic, or proteomic information from donor cells and effecting functional modifications in recipient cells. 11,19,60,61 Whereas most previous studies have focused on these mechanisms as they relate to exosomal pathways in cancer and immune cells, including HCCs, 15,17,18 emerging evidence from this and other laboratories has revealed that fibrogenic cells are also regulated by exosomal networks. 10,22,23,31,34 In addition to revealing that miR-199a-5p targets the CCN2 3 0 -UTR in the same cells as which it is produced, the studies reported here indicate that miR199a-5p is released from HSCs in exosomes and that exosomal miR-199a-5p concentrations reflect those of their producer cells, being expressed at high levels in exosomes from quiescent HSCs and at low levels in exosomes from activated HSCs.…”

Section: Discussionmentioning

confidence: 99%

Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p

Chen

Velazquez

et al. 2016

The American Journal of Pathology

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Pathways of liver fibrosis are controlled by connective tissue growth factor (CCN2). In this study, CCN2 was identified as a target of miR-199a-5p, which was principally expressed in quiescent mouse hepatic stellate cells (HSCs) and directly suppressed production of CCN2. Up-regulated CCN2 expression in fibrotic mouse livers or in activated primary mouse HSCs was associated with miR-199a-5p downregulation. MiR-199a-5p in quiescent mouse HSCs inhibited the activity of a wild-type CCN2 3 0 untranslated region (3 0 -UTR) but not of a mutant CCN2 3 0 -UTR lacking the miR-199a-5p-binding site. In activated mouse HSCs, CCN2, a-smooth muscle actin, and collagen 1(a1) were suppressed by a miR199a-5p mimic, whereas in quiescent mouse HSCs, the inhibited CCN2 3 0 -UTR activity was blocked by a miR-199a-5p antagomir. CCN2 3 0 -UTR activity in human HSCs was reduced by a miR-199a-5p mimic. MiR-199a-5p was present at higher levels in exosomes from quiescent versus activated HSCs. MiR-199a-5pecontaining exosomes were shuttled from quiescent mouse HSCs to activated mouse HSCs in which CCN2 3 0 -UTR activity was then suppressed. Exosomes from quiescent HSCs caused miR-199a-5pe dependent inhibition of CCN2, a-smooth muscle actin, or collagen 1(a1) in activated HSCs in vitro and bound to activated HSCs in vivo. Thus, CCN2 suppression by miR-199a-5p accounts, in part, for lowlevel fibrogenic gene expression in quiescent HSCs and causes dampened gene expression in activated HSCs after horizontal transfer of miR-199a-5p in exosomes from quiescent HSCs. (Am J Pathol 2016, 186: 2921e2933; http://dx

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“…Therefore, it is plausible that EMT and expression of the stem cell markers induced by activation of the TGF-β pathway could be a predictor of unfavorable response of sorafenib in HCC. Another report has shown that the activation of TGF-β induces the expression of stress-responsive long non-coding RNA (lncRNA), which could impair chemotherapy-induced cell death and induce cells positive for the stem cell marker, CD133 [7]. Interestingly, sorafenib also induces stress-responsive lncRNA expression in treated cells [7], suggesting that acquisition of chemoresistance to sorafenib may involve the disruption of TGF-β, a stress-responsive lncRNA.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism and Prediction of Sorafenib Chemoresistance in Human Hepatocellular Carcinoma

Nishida

Kitano

Sakurai

et al. 2015

Dig Dis

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, and prognosis remains unsatisfactory when the disease is diagnosed at an advanced stage. Many molecular targeted agents are being developed for the treatment of advanced HCC; however, the only promising drug to have been developed is sorafenib, which acts as a multi-kinase inhibitor. Unfortunately, a subgroup of HCC is resistant to sorafenib, and the majority of these HCC patients show disease progression even after an initial satisfactory response. To date, a number of studies have examined the underlying mechanisms involved in the response to sorafenib, and trials have been performed to overcome the acquisition of drug resistance. The anti-tumor activity of sorafenib is largely attributed to the blockade of the signals from growth factors, such as vascular endothelial growth factor receptor and platelet-derived growth factor receptor, and the downstream RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade. The activation of an escape pathway from RAF/MEK/ERK possibly results in chemoresistance. In addition, there are several features of HCCs indicating sorafenib resistance, such as epithelial-mesenchymal transition and positive stem cell markers. Here, we review the recent reports and focus on the mechanism and prediction of chemoresistance to sorafenib in HCC.

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Extracellular vesicle‐mediated transfer of long non‐coding RNA ROR modulates chemosensitivity in human hepatocellular cancer

Cited by 383 publications

References 31 publications

Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p

Molecular Mechanism and Prediction of Sorafenib Chemoresistance in Human Hepatocellular Carcinoma

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Extracellular vesicle‐mediated transfer of long non‐coding RNA ROR modulates chemosensitivity in human hepatocellular cancer

Cited by 383 publications

References 31 publications

Cisplatin-resistant lung cancer cell&ndash;derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100&ndash;5p-dependent manner

Cisplatin-resistant lung cancer cell&ndash;derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100&ndash;5p-dependent manner

Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p

Molecular Mechanism and Prediction of Sorafenib Chemoresistance in Human Hepatocellular Carcinoma

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Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner