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外泌体传递的长非编码 RNA PTENP1 抑制膀胱癌进展。

Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression.

机构信息

Department of Environmental Genomics, School of Public Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.

Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Mol Cancer. 2018 Oct 3;17(1):143. doi: 10.1186/s12943-018-0880-3.

Abstract

BACKGROUND

Extracellular communication within the tumor microenvironment plays a critical role in tumor progression. Although exosomes can package into long non-coding RNAs (lncRNAs) to mediate extracellular communication, the role of exosomal lncRNA PTENP1 in bladder cancer (BC) remains unclear.

METHOD

We detected PTENP1 expression between patients with BC and healthy controls; the expression occurred in tissues and exosomes from plasma. We assessed the diagnostic accuracy by the receiver operating characteristic curve (ROC) and the area under curve (AUC). Cell phenotypes and animal experiments were performed to determine the effect of exosomal PTENP1.

RESULTS

PTENP1 was significantly reduced in BC tissues and in exosomes from plasma of patients with BC (P < 0.05). We found that PTENP1 was mainly wrapped by exosomes. Exosomal PTENP1 could distinguish patients with BC from healthy controls (AUC = 0.743; 95% confidence interval (CI) = 0.645-0.840). Normal cells secreted exosomal PTENP1 and transmitted it to BC cells, thus inhibiting the biological malignant behavior of BC cells by increasing cell apoptosis and reducing the ability to invade and migrate (P < 0.05). Exosomal PTENP1 could suppress tumor growth in vivo. Furthermore, exosomal PTENP1 mediated the expression of PTEN by competitively binding to microRNA-17.

CONCLUSION

Exosomal PTENP1 is a promising novel biomarker that can be used for the clinical detection of BC. Exosomes derived from normal cells transfer PTENP1 to BC cells, which reduce the progression of BC both in vitro and in vivo and suggest that exosomal PTENP1 participates in normal-cell-to-bladder-cell communication during the carcinogenesis of BC.

摘要

背景

肿瘤微环境中的细胞外通讯在肿瘤进展中起着关键作用。尽管外泌体可以将长链非编码 RNA(lncRNA)包裹起来,从而介导细胞外通讯,但外泌体 lncRNA PTENP1 在膀胱癌(BC)中的作用尚不清楚。

方法

我们检测了 BC 患者和健康对照者之间 PTENP1 的表达;在组织和血浆来源的外泌体中检测了其表达。我们通过接受者操作特征曲线(ROC)和曲线下面积(AUC)评估了诊断准确性。进行细胞表型和动物实验以确定外泌体 PTENP1 的作用。

结果

BC 组织和 BC 患者血浆来源的外泌体中 PTENP1 的表达明显降低(P<0.05)。我们发现 PTENP1 主要被外泌体包裹。外泌体 PTENP1 可以区分 BC 患者和健康对照者(AUC=0.743;95%置信区间(CI)=0.645-0.840)。正常细胞分泌含有 PTENP1 的外泌体并将其传递给 BC 细胞,从而通过增加细胞凋亡和降低侵袭和迁移能力来抑制 BC 细胞的生物学恶性行为(P<0.05)。外泌体 PTENP1 可以在体内抑制肿瘤生长。此外,外泌体 PTENP1 通过竞争性结合 microRNA-17 来调节 PTEN 的表达。

结论

外泌体 PTENP1 是一种很有前途的新型生物标志物,可用于 BC 的临床检测。来自正常细胞的外泌体将 PTENP1 转移到 BC 细胞,这在体外和体内都降低了 BC 的进展,并提示外泌体 PTENP1 参与了 BC 发生过程中正常细胞与膀胱细胞之间的通讯。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8d2/6169076/e1f224e06dd9/12943_2018_880_Fig1_HTML.jpg

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