当前位置: X-MOL 学术Cell Death Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-09-09 , DOI: 10.1038/s41419-020-02926-8
Fang Dong 1 , Shengnan Ruan 1 , Jinlong Wang 2 , Yun Xia 3 , Kehao Le 1 , Xiaoyun Xiao 1 , Ting Hu 3 , Qiong Wang 3
Affiliation  

As a common female malignancy, triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancers (BC). This study further studied the role of long noncoding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) in TNBC. Functional assays, including EdU, wound healing, transwell, and immunofluorescence staining, revealed the effect of PCAT6 on cell proliferation, migration, and EMT process. The tube-formation assay disclosed the function of PCAT6 on angiogenesis. In vivo assays were also established to explore the impact of PCAT6 on tumor growth and microangiogenesis. The results revealed that PCAT6 boosted TNBC cell proliferation, migration, and angiogenesis both in vitro and in vivo. Then, this study unveiled that M2 macrophage secreted VEGF to stimulate the upregulation of PCAT6, thus promoting angiogenesis in TNBC. Next, through bioinformatics analysis and mechanism assays, we identified that PCAT6 positively regulated VEGFR2 expression via ceRNA pattern and then participated in VEGFR/AKT/mTOR signaling pathway to accelerate angiogenesis. Moreover, PCAT6 bound USP14, a deubiquitinase, to induce the deubiquitination of VEGFR2. On the whole, M2 macrophage-induced upregulation of PCAT6 facilitates TNBC tumorigenesis through modulation of VEGFR2 expression via ceRNA and deubiquitination patterns.



中文翻译:

M2巨噬细胞诱导的lncRNA PCAT6通过调节VEGFR2促进三阴性乳腺癌的肿瘤发生和血管生成。

三阴性乳腺癌(TNBC)作为一种常见的女性恶性肿瘤,是乳腺癌(BC)中恶性程度最高的亚型。本研究进一步研究了长链非编码 RNA (lncRNA) 前列腺癌相关转录本 6 (PCAT6) 在 TNBC 中的作用。包括 EdU、伤口愈合、transwell 和免疫荧光染色在内的功能测定揭示了 PCAT6 对细胞增殖、迁移和 EMT 过程的影响。管形成测定揭示了PCAT6对血管生成的功能。还建立了体内测定以探索 PCAT6 对肿瘤生长和微血管生成的影响。结果表明,PCAT6 在体外和体内都促进了 TNBC 细胞增殖、迁移和血管生成。然后,本研究揭示了 M2 巨噬细胞分泌 VEGF 以刺激 PCAT6 的上调,从而促进 TNBC 中的血管生成。接下来,通过生物信息学分析和机制分析,我们发现 PCAT6 通过 ceRNA 模式正向调节 VEGFR2 表达,然后参与 VEGFR/AKT/mTOR 信号通路以加速血管生成。此外,PCAT6 与去泛素酶 USP14 结合,诱导 VEGFR2 去泛素化。总体而言,M2 巨噬细胞诱导的 PCAT6 上调通过 ceRNA 和去泛素化模式调节 VEGFR2 表达来促进 TNBC 肿瘤发生。

更新日期:2020-09-10
down
wechat
bug