Dataset Information

Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

ABSTRACT: BACKGROUND:Oxidized low density lipoprotein receptor 1 (OLR1), a type II membrane protein, has been identified as receptor for oxidized low-density lipoprotein. The current study firstly provided evidence that OLR1 regulated EMT and thus promoted lung metastases in osteosarcoma (OS). METHOD:All relevant experiments were conducted according to the manufacturer's protocols. In vivo tumor xenograft experiments were carried out in 6- to 16-week-old mice, then maintained in our animal facility under pathogen-free conditions in accordance with the Institutional Guidelines and approval by local authorities. For the use of the clinical materials for research purposes, prior patient's consent and approval from the Institute Research Ethics Committee were obtained. All statistical analyses were performed using IBM SPSS Statistics 22.0 for Windows. RESULT:Microarrays were adopted to explore the underlying epigenetic mechanisms related to metastasis. 11 genes were identified among total 26,890 differentially expressed genes. After validated in paired primary and metastatic tissues, OLR1 was selected in the current study. The expression levels of OLR1 were tested in 4 widely used cell lines. Cell proliferation, migration and invasion could be enhanced when OLR1 was overexpressed. OLR1 overexpression also triggered G1 to S?+?G2 phases of cell cycle. Accordingly, cell proliferations, migration and invasion would be reduced when OLR1 was silenced. OLR1-silencing blocked G1 to S?+?G2 phases of cell cycle. Also, OLR1 silencing effectively suppressed local tumor carcinogenesis and lung metastases in vivo. Moreover, silencing OLR1 repressed the expression of mesenchymal markers (Snail, Twist, and N-cadherin), but induced an epithelial marker (E-cadherin). CONCLUSION:This study indicated a novel molecular mechanism involving the role of OLR1 in lung metastases of osteosarcoma, strengthened the correlation between OLR1 and lung metastases.

SUBMITTER: Jiang L

PROVIDER: S-EPMC6852786 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

Jiang Long L Jiang Shanshan S Zhou Wenjie W Huang Jia J Lin Yongbin Y Long Hao H Luo Qingquan Q

Journal of translational medicine 20191112 1

<h4>Background</h4>Oxidized low density lipoprotein receptor 1 (OLR1), a type II membrane protein, has been identified as receptor for oxidized low-density lipoprotein. The current study firstly provided evidence that OLR1 regulated EMT and thus promoted lung metastases in osteosarcoma (OS).<h4>Method</h4>All relevant experiments were conducted according to the manufacturer's protocols. In vivo tumor xenograft experiments were carried out in 6- to 16-week-old mice, then maintained in our animal ...[more]

PMID: 31718700

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Project description:BackgroundMetastatic bladder cancer (BLCA) is a lethal disease with an unmet need for study. Transgelin (TAGLN) is an actin-binding protein that affects the dynamics of the actin cytoskeleton indicating its robust potential as a metastasis initiator. Here, we sought to explore the expression pattern of TAGLN and elucidate its specific functioning and mechanisms in BLCA.MethodsA comprehensive assessment of TAGLN expression in BLCA was performed in three cohorts with a total of 847 patients. The potential effects of TAGLN on BLCA were further determined using clinical genomic analyses that guided the subsequent functional and mechanistic studies. In vitro migration, invasion assays and in vivo metastatic mouse model were performed to explore the biological functions of TAGLN in BLCA cells. Immunofluorescence, western blot and correlation analysis were used to investigate the molecular mechanisms of TAGLN.FindingsTAGLN was highly expressed in BLCA and correlated with advanced prognostic features. TAGLN promoted cell colony formation and cell migration and invasion both in vitro and in vivo by inducing invadopodia formation and epithelial-mesenchymal transition, during which a significant correlation between TAGLN and Slug was observed. The progression-dependent correlation between TGF-β and TAGLN was analysed at both the cellular and tissue levels, while TGF-β-mediated migration was abolished by the suppression of TAGLN.InterpretationOverall, TAGLN is a promising novel prognosis biomarker of BLCA, and its metastatic mechanisms indicate that TAGLN may represent a novel target agent that can be utilized for the clinical management of invasive and metastatic BLCA. FUND: This work was supported by the National Natural Science Foundation of China [81772703, 81672546, 81602253]; the Natural Science Foundation of Beijing [71772219, 7152146]. and Innovative Fund for Doctoral Students of Peking University Health Science Center (BUM2018BSS002). Funders had no role in the design of the study, data collection, data analysis, interpretation, or the writing of this report.

Project description:Background:Lung cancer is the most common and lethal malignancy worldwide. TCTP is highly expressed in various cancers including lung cancer. Epithelial-mesenchymal transition (EMT) could increase cancer cell invasion. Whether TCTP's expression is associated with EMT in lung adenocarcinoma is largely unknown. Methods:Several Gene Expression Omnibus datasets were used to analyze the correlation between TCTP expression and overall survival of lung adenocarcinoma patients by Kaplan-Meier survival analysis. Then, 24 surgically removed fresh lung adenocarcinoma tissue samples and paired paracancer tissue samples were used to analyze the correlation between TCTP expression and tumor stage by immunohistochemical analysis. Furthermore, stable cell lines were generated using lentiviral transduction systems to knock down or overexpress TCTP in A549 cells. Cell migration and invasion were measured by scratch and transwell assays, and EMT marker proteins such as ?-SMA, ZEB1, and E-cadherin were quantitated by Western blot. The expression levels of miR-200a, miR-141, and miR-429 were determined by real-time quantitative PCR, and their target genes were predicted by an online database miRTarBase. The interaction between TCTP and these genes was analyzed by String database and visualized by Cytoscape. Results:TCTP was highly expressed in tumor tissues compared to paracancer tissues. The expression of TCTP was associated with shorter overall survival. TCTP knockdown experiment in A549 cells suggested that TCTP knockdown could decrease the migration and invasion of lung cancer cells, and the expression level of ZEB1 and ?-SMA, but increase the expression of E-cadherin and p53. Vice versa, overexpression of TCTP could increase the migration and invasion of cancer cells, and the expression level of ZEB1 and ?-SMA, but decrease the expression of E-cadherin and p53. Furthermore, we found the expression of miR-200a, miR-141, and miR-429 was associated with TCTP expression. Conclusion:TCTP promotes EMT in lung adenocarcinoma, and this effect may be associated with miR-200 family members like miR-200a, miR-141, and miR-429.

Dataset Information

Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

Publications

Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

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