Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells

Zhang, Jian; Shan, Weifeng; Jin, Te-te; Wu, Guojun; Xiong, Xiaoxing; Huang, Jin; Zhu, Shengmei

doi:10.1186/s12967-014-0279-x

Cited by 87 publications

(84 citation statements)

References 27 publications

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“…Microvesicles derived from liver stem cells inhibit HCC cell growth and this is mediated by various miRNAs contained in those microvesicles [31]. An intravenous anesthetic propofol has antitumor effects, and it has been shown that mice with propofol administration secrete macrophage-derived microvesicles and those microvesicles and their cargo miR-142-3p significantly inhibits tumor growth in vivo [32]. In liver cancers such as HCC, malignant cells can not only modify microenvironment to help their proliferation and invasion, but also be controlled by other cells via cell-cell communication using exosomes and microvesicles (Figure 4).…”

Section: Exosomes As Therapeutic Tools For Liver Diseasesmentioning

confidence: 99%

Exosomes in liver pathology

Sato

Meng²,

Glaser

et al. 2016

Journal of Hepatology

159

145

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Exosomes are small (~100 nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, anti-viral infection and hepatocyte regeneration, indicating that exosomes have great potential development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology.

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Section: Exosomes As Therapeutic Tools For Liver Diseasesmentioning

confidence: 99%

Exosomes in liver pathology

Sato

Meng²,

Glaser

et al. 2016

Journal of Hepatology

159

145

View full text Add to dashboard Cite

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“…Previous studies have suggested that microRNAs (miRNAs) are involved in mediating the effects of propofol on anti-cancers, including miR-199a, miR-142-3p, miR-143 and let-7 (13)(14)(15)24,25). Propofol can influence the expression of these miRNAs, which in turn are able to regulate their target mRNAs to affect the behavior of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Zhang et al investigated the effect of propofol on liver cancer and found that propofol can effectively inhibit the proliferation and invasiveness of HCC cells, and induce apoptosis, in vitro (13,14). In addition, Zhang et al demonstrated that propofol can inhibit tumor growth in tumor-bearing mice by activation of macrophages, thus exerting a therapeutic effect on HCC in vivo (15). However, the molecular mechanisms underlying the antitumor function of propofol on HCC has not been elucidated until now.…”

Section: Introductionmentioning

confidence: 99%

Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2-mediated Wnt/β-catenin pathway

Zou

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Propofol is a commonly used intravenous anesthetic in tumor surgery. Recently, studies have confirmed that propofol has an antitumor effect on hepatocellular carcinoma (HCC); however, the molecular mechanism underlying this effect has not been elucidated until now. The present study aimed to investigate the mechanism of propofol on HepG2 cell proliferation, apoptosis and invasion, focusing on High Mobility Group AT-Hook 2 (HMGA2)-mediated Wnt/β-catenin pathway. The HepG2 cells were treated with various concentrations of propofol for 24 h, the relative protein levels of HMGA2, Wnt3a, β-catenin, Snail Family Zinc Finger 1 and c-myc were determined by western blot analysis. HMGA2-pcDNA3.1 plasmid was transfected into the HepG2 cells to overexpress HMGA2. Cell proliferation, apoptosis and invasion were examined by MTT assays, flow cytometry and Transwell-matrigel invasion assays, respectively. The results showed that propofol suppressed HMGA2 expression and Wnt/β-catenin signaling in a dose-dependent manner. Propofol was able to inhibit cell proliferation and invasion, and induce cell apoptosis of HepG2 cells; however, these effects were attenuated by HMGA2 overexpression. The suppressed Wnt/β-catenin signaling in HepG2 cells by treatment with propofol was also reversed by HMGA2 overexpression. In conclusion, this study provided a novel mechanism underlying the anti-tumor function of propofol on HCC. To the best of our knowledge, the present study is the first to demonstrate that propofol could downregulate the expression of HMGA2, which inhibited the Wnt/β-catenin pathway, thus leading to the inhibition of cell proliferation and invasion, as well as the apoptosis of HepG2 cells.

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“…Animals bearing tumors were treated with anti-tumor propofol. The downregulation of miR-142-3p in TAMs using its inhibitor reversed the effect of propofol on hepatocellular carcinoma cells [166].…”

Section: Macrophage-derived Mirs-an Arm Of a Sentinelmentioning

confidence: 97%

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

Syed

Frank

Raue

et al. 2019

Cells

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MicroRNAs (miRs) significantly contribute to the regulation of gene expression, by virtue of their ability to interact with a broad, yet specific set of target genes. MiRs are produced and released by almost every cell type and play an important role in horizontal gene regulation in the tumor microenvironment (TME). In the TME, both tumor and stroma cells cross-communicate via diverse factors including miRs, which are taking central stage as a therapeutic target of anti-tumor therapy. One of the immune escape strategies adopted by tumor cells is to release miRs as a Trojan horse to hijack circulating or tumor-localized monocytes/macrophages to tune them for pro-tumoral functions. On the other hand, macrophage-derived miRs exert anti-tumor functions. The transfer of miRs from host to recipient cells depends on the supramolecular structure and composition of miR carriers, which determine the distinct uptake mechanism by recipient cells. In this review, we provide a recent update on the miR-mediated crosstalk between tumor cells and macrophages and their mode of uptake in the TME.(TNF-α), and provoke the secretion of pro-inflammatory cytokines including interleukin-1 (IL-1), IL-6, IL-12, IL-23, and TNF-α and reactive nitrogen and oxygen intermediates (RNI, ROI) [5]. In contrast, anti-inflammatory stimuli such as IL-4, IL-13, IL-10, and glucocorticoid or immune complexes (IC) plus LPS induce macrophages to an M2 phenotype. This type is characterized by a decreased production of pro-inflammatory cytokines, increased production of anti-inflammatory cytokines (e.g., IL-10), and factors that mediate immunosuppression and tissue remodeling. M2 macrophages have been divided into further subgroups. The M2a type is generated in response to IL-3 and IL-13, while M2b macrophages respond to immune complexes and Toll-like receptor (TLR) activation. M2c macrophages represent deactivated macrophages that suppress pro-inflammatory cytokines, while the M2d type represents a regulatory macrophage [6] that is often grouped with TAMs [5,7,8]. In line with these varied responses, Janus-faced macrophage functions are largely determined by their microenvironment rather than their genetic imprint [9,10]. In tumors and during the resolution of inflammation, hijacked macrophages attain pro-tumor or wound healing phenotypes due to tumor-derived factors [11], which emerge as a target for tumor therapy [12,13]. TAMs expressing classical activation markers produce pro-inflammatory cytokines and reactive oxygen species (ROS) and, thus, are crucial for tumor cell killing [14,15]. The high degree of plasticity demonstrated by macrophages in pathological conditions can be attributed to a) dynamic regulation of gene expression and b) rapid activation of signaling cascades that determine their effector functions. Signaling cascades triggered by local environmental cues and controlling the transcriptional machinery, ultimately determine the effector functions of macrophages in the tumor microenvironment (TME). Hence, understanding and modulating these ...

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Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells

Cited by 87 publications

References 27 publications

Exosomes in liver pathology

Exosomes in liver pathology

Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2-mediated Wnt/β-catenin pathway

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

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