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LncRNA RP11-361F15.2 promotes osteosarcoma tumorigenesis by inhibiting M2-Like polarization of tumor-associated macrophages of CPEB4.

LncRNA RP11-361F15.2 通过抑制 cpeb4 的肿瘤相关巨噬细胞的 M2-Like 极化促进骨肉瘤肿瘤发生。

  • 影响因子:6.50
  • DOI:10.1016/j.canlet.2019.12.041
  • 作者列表:"Yang D","Liu K","Fan L","Liang W","Xu T","Jiang W","Lu H","Jiang J","Wang C","Li G","Zhang X
  • 发表时间:2020-03-31
Abstract

:Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.

摘要

: 长链非编码 rna (lncRNA) 调控骨肉瘤 (OS) 的启动和进展,特别是 lncRNA RP11-361F15.2 已被证明在肿瘤发生中起着突出的作用。以前,肿瘤相关巨噬细胞 (TAMs) 的 M2-Like 极化已被确定在癌症迁移/侵袭中起关键作用。因此,了解 RP11-361F15.2 在肿瘤发生中的作用及其与 TAMs 极化 M2-Like 关联至关重要。结果表明,RP11-361F15.2 在 OS 组织中显著升高,其表达与胞浆多聚腺苷酸化元件结合蛋白 4 (CPEB4) 表达呈正相关,与 miR-30c-5p 表达呈负相关。此外,RP11-361F15.2 的过表达增加了 OS 细胞迁移/侵袭和 TAMs 在体外的 M2-Like 极化,以及促进体内异种移植肿瘤的生长。从机理上讲,荧光素酶报告基因检测表明,RP11-361F15.2 通过竞争性结合 miR-30c-5p 上调 CPEB4 的表达。此外,我们已经确定 RP11-361F15.2 通过 OS 中的 CPEB4-mediated 促进 M2-Like 的肿瘤发生和 TAMs 的 miR-30c-5p 极化。我们还确定 RP11-361F15.2 作为竞争性内源性 RNA (ceRNA) 对抗 miR-30c-5p,从而结合和激活 cpeb4。该 RP11-361F15.2/miR-30c-5p/CPEB4 环可作为 OS 的潜在治疗策略。

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影响因子:2.87
发表时间:2020-01-31
来源期刊:Bioscience reports
DOI:10.1042/BSR20191251
作者列表:["Ying T","Dong JL","Yuan C","Li P","Guo Q"]

METHODS:BACKGROUND:Osteosarcoma is the most common primary bone malignancy in children and adolescents. In order to find factors related to its recurrence, and thus improve recovery prospects, a powerful clinical signature is needed. Long noncoding RNAs (lncRNAs) are essential in osteosarcoma processes and development, and here we report significant lncRNAs to aid in earlier diagnosis of osteosarcoma. METHODS:A univariate Cox proportional hazards regression analysis and a multivariate Cox regression analysis were used to analyze osteosarcoma patients' lncRNA expression data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET), a public database. RESULTS:A lncRNA signature consisting of three lncRNAs (RP1-261G23.7, RP11-69E11.4 and SATB2-AS1) was selected. The signature was used to sort patients into high-risk and low-risk groups with meaningful recurrence rates (median recurrence time 16.80 vs. >128.22 months, log-rank test, P143.80 months, log-rank test, P=0.006). A multivariate Cox regression analysis showed that the significant lncRNA was an independent prognostic factor for osteosarcoma patients. Functional analysis suggests that these lncRNAs were related to the PI3K-Akt signaling pathway, the Wnt signaling pathway, and the G-protein coupled receptor signaling pathway, all of which have various, important roles in osteosarcoma development. The significant 3-lncRNA set could be a novel prediction biomarker that could aid in treatment and also predict the likelihood of recurrence of osteosarcoma in patients.

翻译标题与摘要 下载文献
影响因子:6.50
发表时间:2020-03-31
来源期刊:Cancer letters
DOI:10.1016/j.canlet.2019.12.041
作者列表:["Yang D","Liu K","Fan L","Liang W","Xu T","Jiang W","Lu H","Jiang J","Wang C","Li G","Zhang X"]

METHODS::Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.

翻译标题与摘要 下载文献
影响因子:11.08
发表时间:2020-01-13
DOI:10.1200/JCO.19.00827
作者列表:["Kelley LM","Schlegel M","Hecker-Nolting S","Kevric M","Haller B","Rössig C","Reichardt P","Kager L","Kühne T","Gosheger G","Windhager R","Specht K","Rechl H","Tunn PU","Baumhoer D","Wirth T","Werner M","von Kalle T","Nathrath M","Burdach S","Bielack S","von Lüttichau I"]

METHODS:PURPOSE:The objective of this study was to investigate potential correlations between pathologic fractures (PFs) and prognosis of patients with primary central high-grade osteosarcoma of the extremities. METHODS:We retrospectively analyzed 2,847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database with primary central high-grade osteosarcoma of the extremities, treated between 1980 and 2010. Intended treatment included pre- and postoperative chemotherapy and surgery. Univariable and multivariable survival analyses were performed for all patients and then differentiated for adult and pediatric (≤ 18 years at time of diagnosis) patients. RESULTS:A total of 2,193 patients were ≤ 18 years of age; 11.3% of all patients had PFs. In the overall cohort, presence of PF correlated significantly with tumor site, histologic subtype, relative tumor size, and primary metastases, but not with body mass index or local surgical remission. In univariable analysis, 5-year overall survival (OAS) of patients with and without PF was 63% versus 71%, respectively (P = .007), and 5-year event-free survival (EFS) was 51% versus 58% (P = .026). In pediatric patients, OAS and EFS did not differ significantly between patients with and without PF. In adults, 5-year OAS in patients with and without PF was 46% versus 69% (P < .001), and 5-year EFS was 36% versus 56% (P < .001). In multivariable analysis, PF was not a statistically significant factor for OAS or EFS in the total cohort or in pediatric patients. In adult patients, PF remained an independent prognostic factor for OAS (P = .013; hazard ratio [HR], 1.893). It was not a significant prognostic factor for EFS (P = .263; HR, 1.312). CONCLUSION:In this largest study to date with extremity osteosarcomas, we observed the occurrence of PF to correlate with inferior OAS expectancies in adult but not in pediatric patients.

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