Abstract:
Introduction:Hypoxia and tumor-associated macrophage (TAM) are key regulators in remodeling the microenvironment of esophageal squamous cell carcinoma (ESCC). Hypoxia could stimulate tumor cells to secrete more exosomes and activate TAMs to M2 type. Here, we investigated the function and the underlying mechanism of tumor-derived exosomal hsa-circ-0048117 in TAM polarization in ESCC. Collectively, these data indicate that PC cells generate miR-301a-3p-rich exosomes in a hypoxic microenvironment, which then polarize macrophages to promote malignant behaviors of PC cells. Methods:Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were used to analyze the physical characteristics of exosomes. High-throughput sequencing and bioinformatic analysis were performed to screen the potential exosomal circRNA. FISH, Ago2 RIP, pull-down and dual-luciferase reporter assay were conducted to figure out the correlation among hsa-circ-0048117, miR-140 and toll-like receptor 4 (TLR4). Flow cytometry and Western blot were used to evaluate their joint effect in macrophages polarization. Then, the invasion and migration ability were evaluated by transwell experiment. At last, serum exo-hsa-circ-0048117 in ESCC patients was compared and the correlation between its expression and T stage, N stage and TNM grades was analyzed. Results:Hsa-circ-0048117 was significantly upregulated and enriched in exosomes secreted by hypoxia pre-challenged tumor cells and contributed to M2 macrophage polarization. Hsa-circ-0048117 depletion in macrophage led to inhibition of M2 polarization while restoration of hsa-circ-0048117 could rescue the process. Moreover, hsa-circ-0048117 could act as sponge of miR-140 by competing with TLR4 to facilitate the M2 macrophage polarization. Exo-hsa-circ-0048117 could be transmitted to macrophages to promote M2 polarization and M2 macrophages could enhance the ability of invasion and migration of tumor cells by secreting Arg1, IL-10 and TGF-β. Higher serum exo-hsa-circ-0048117 predicted an advanced T and N stage and positively correlated with TNM grade. Conclusion:Our findings indicated that ESCC cells generate hsa-circ-0048117-rich exosomes in a hypoxic microenvironment; hsa-circ-0048117 was believed to promote M2 macrophage polarization which favors the malignant behaviors of ESCC cells. These results reminded us that exosomal hsa-circ-0048117 may play a key role in remodeling the microenvironment and modulating progression in ESCC.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Lu Q,Wang X,Zhu J,Fei X,Chen H,Li Cdoi
10.2147/OTT.S284192subject
Has Abstractpub_date
2020-11-18 00:00:00pages
11883-11897issn
1178-6930pii
284192journal_volume
13pub_type
杂志文章abstract:BACKGROUND:Pancreatic cancer is one of the most aggressive and intractable malignant tumors, and most deaths from pancreatic cancer are related to metastases. It has been demonstrated in vitro that overexpression of programmed death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue (PTEN) expr...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S130481
更新日期:2017-04-12 00:00:00
abstract::[This corrects the article on p. 5203 in vol. 9, PMID: 27578986.]. ...
journal_title:OncoTargets and therapy
pub_type: 已发布勘误
doi:10.2147/OTT.S139588
更新日期:2017-04-27 00:00:00
abstract:Background:Gastric cancer (GC) is one of the most common malignant tumors and the second most frequent cause of cancer death worldwide. Crocin is a kind of bioactive constituent found in the stigmas of saffron, which has shown various pharmacological activities. Methods:In this study, we investigated the inhibitory ef...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S254167
更新日期:2021-01-07 00:00:00
abstract:Background:Patients with BRAF (v-Raf murine sarcoma viral oncogene homolog B) V600E-mutated metastatic colorectal cancer (mCRC) have a poor prognosis. The Southwest Oncology Group (SWOG) 1406 study evaluated the efficacy of vemurafenib in combination with irinotecan and cetuximab for simultaneous inhibition of epiderma...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S180845
更新日期:2019-01-08 00:00:00
abstract:Background/Aims:The effects of lncRNA-NORAD/mir-520a-3p on proliferation and invasion of non-small cell lung cancer (NSCLC) were studied, and its potential molecular mechanism was discussed. Methods:qRT-PCR was used to detect the expression of lncRNA NORAD and miR-520a-3p in non-small cell lung cancer tissues and cell...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S230954
更新日期:2020-02-19 00:00:00
abstract::The mitogen-activated protein kinase (MAPK) pathway is a critical oncogenic driver signal in a number of malignancies. The discovery of activating mutations in the MAPK pathway has led to the development of MAPK pathway inhibitors. Selumetinib is a potent and selective inhibitor of MEK1 and MEK2, which are essential d...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S51596
更新日期:2014-09-19 00:00:00
abstract:Background:The neutrophil-lymphocyte ratio (NLR), a biomarker for systematic inflammation, has been recently identified as a prognostic factor for various types of both solid and hematologic malignancies. Our study presented here was the first meta-analysis assessing the prognostic role of NLR in multiple myeloma (MM)....
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S153146
更新日期:2018-01-23 00:00:00
abstract:BACKGROUND:Experimental disruption of the telomere overhang induces a potent DNA damage response and is the target of newly emerging cancer therapeutics. Introduction of T-oligo, an eleven-base oligonucleotide homologous to the 3'-telomeric overhang, mimics telomere disruption and induces DNA damage responses through a...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S54575
更新日期:2013-12-18 00:00:00
abstract:Purpose:Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and its incidence continues to rise yearly. Photodynamic therapy (PDT) is a non-invasive form of cancer therapy, which utilizes the combined action of a photosensitizer, light, and oxygen molecules to selectively cause cellul...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S228792
更新日期:2019-12-31 00:00:00
abstract::Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTL...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S57335
更新日期:2014-02-19 00:00:00
abstract::Increasing evidence has shown that aldehyde dehydrogenase 1A1 (ALDH1A1), a detoxifying enzyme, is responsible for chemoresistance in a variety of tumors. Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), che...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S107957
更新日期:2016-08-29 00:00:00
abstract:BACKGROUND:The prognostic value of inflammatory index in esophageal cancer (EC) has not been established. In the present study, therefore, we initially evaluated a novel prognostic system, named the COCC (COmbination of C-reactive protein [CRP] and carcinoembryonic antigen [CEA]), for making a prognosis in patients wit...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S77378
更新日期:2015-04-10 00:00:00
abstract::Gastric cancer (GC) is one of the leading causes of tumor-related mortality. In addition to surgery and endoscopic resection, systemic therapy remains the main treatment option for GC, especially for advanced-stage disease and for cases not suitable for surgical therapy. Hence, improving the efficacy of systemic thera...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S221354
更新日期:2019-12-24 00:00:00
abstract:Purposes:The main aim of the study was to investigate the dosimetric difference between acuros XB algorithm (AXB), anisotropic analytic algorithm (AAA), and pencil beam convolution (PBC) algorithm in stereotactic body radiation therapy (SBRT) plan for non-small cell lung cancer (NSCLC). Patients and Methods:Thirty-eig...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S201473
更新日期:2019-08-12 00:00:00
abstract:BACKGROUND:This meta-analysis aimed to assess available evidence on possible associations of interleukin-28B polymorphisms rs8099917 and rs12979860 with development of hepatitis virus-related hepatocellular carcinoma (HCC). METHODS:PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure datab...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S104904
更新日期:2016-05-30 00:00:00
abstract:BACKGROUND:Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) is identified to be overexpressed in several cancers. However, the role of MALAT-1 in chondrosarcoma is poorly understood. METHODS:The expression of MALAT-1 and Notch-1 signaling pathway was detected in chondrosarcoma tissues and chondrosarcom...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S100003
更新日期:2016-04-13 00:00:00
abstract::The incidence rate of breast cancers in People's Republic of China has increased in the last decade, and many cases are responsive to hormone therapies. The third-generation aromatase inhibitor letrozole inhibits estrogen production, and is more efficacious than the estrogen receptor inhibitor tamoxifen. In recent yea...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S81087
更新日期:2016-03-01 00:00:00
abstract:Purpose:Intraoperative identification of rectal cancer (RC) can be challenging, especially because of fibrosis after treatment with preoperative chemo- and radiotherapy (CRT). Tumor-targeted fluorescence imaging can enhance the contrast between tumor and normal tissue during surgery. Promising targets for RC imaging ar...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S145473
更新日期:2018-03-23 00:00:00
abstract::Background: Altered expression of the BCL-2 family member MCL-1 has been linked to the progression and outcome of various malignancies. Recently, MCL-1 inhibitor S63845 was reported to kill MCL-1-dependent cancer cells and has potential value in clinical application. Purpose: Herein, we reported MCL-1 expression patte...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S194549
更新日期:2019-05-01 00:00:00
abstract::This retrospective study was conducted to evaluate the prognostic significance of the preoperative plasma D-dimer levels and platelet counts in patients with pancreatic adenocarcinoma. A total of 168 consecutive locally advanced pancreatic adenocarcinoma patients who underwent intensity modulated radiation therapy wit...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S82329
更新日期:2015-06-04 00:00:00
abstract::Multiple drug resistance is still an unsolved problem in cancer therapy. Our previous study demonstrated that the chemotherapeutic drug doxorubicin (Dox) induced upregulation of P-glycoprotein (P-gp) in endothelial cells, resulting in a 20-fold increase in drug resistance and reduced efficiency of Dox treatment in a m...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S67251
更新日期:2014-12-04 00:00:00
abstract:PURPOSE:The prognostic significance of circulating tumor cells (CTCs) in esophageal carcinoma (EC) is controversial. We aim to assess its association with clinicopathological and prognostic relevance in EC by using a meta-analysis. METHODS:We searched PubMed, Cochrane Database, Embase databases, and the references in ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S100005
更新日期:2016-03-31 00:00:00
abstract:Purpose:Here, we investigated the involvement of the miR-188-5p/inhibitor of the DNA binding 4 (ID4) axis in retinoblastoma (Rb). Patients and methods:We included 35 Rb tissues and the corresponding adjacent normal tissues. RT-qPCR, Western blot, lentivirus transfection, measurement of cell migration in vitro, and chi...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S229739
更新日期:2019-11-27 00:00:00
abstract:Purpose:Programmed death ligand 1 (PD-L1) is widely used for predicting immune checkpoint inhibitors but has a limited effect on predicting clinical response. The aim of this study was to examine the prognostic value and PD-1 inhibitor therapeutic efficiency of SNX20 in lung adenocarcinoma. Methods:We evaluated the mR...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S262909
更新日期:2020-10-09 00:00:00
abstract:Introduction:Melanoma is a common skin cancer that is usually associated with poor clinical outcomes. Recently, the immune checkpoint GITR has been identified as a promising target for immunotherapy of melanoma. In this study, we aimed to investigate the post-translational regulation mechanism of GITR in melanoma. Met...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S212317
更新日期:2019-12-04 00:00:00
abstract::Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical an...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/ott.s3027
更新日期:2009-02-18 00:00:00
abstract::Patients diagnosed as lung adenocarcinoma with brain metastasis usually result in poor prognosis with limited survival time. Palliative systematic therapy has emerged as the primary choice for non-small cell lung cancer patients with brain metastasis harboring wild-type drive genes. However, the objective response rat...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S226735
更新日期:2019-11-11 00:00:00
abstract:Purpose:Stomach cancer is one of the highest incidence and mortality malignancies worldwide. Our study aimed to illustrate the somatic mutation landscape and identify molecular markers of stomach cancer. Materials and Methods:By integrated analysis of sequencing data and clinical data of stomach adenocarcinoma (STAD) ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S263733
更新日期:2020-08-04 00:00:00
abstract:OBJECTIVE:To investigate the impact of surgical resection extent on the postoperative complications and the prognosis in patients with stage II endometrial cancer. METHODS:A total of 54 patients were retrospectively reviewed, 35 patients underwent subradical hysterectomy and 19 patients received radical hysterectomy, ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S95806
更新日期:2016-02-16 00:00:00
abstract:Background:LncRNA EMX2OS (EMX2 opposite strand/antisense RNA) is notably downregulated in prostate cancer (PCa) tissues and may be regarded as a potential molecular biomarker for diagnosis and prognosis. However, its exact role in regulating the development of PCa is obscure. Methods:The EMX2OS expression was assessed...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S243552
更新日期:2020-07-21 00:00:00