Golgi phosphoprotein 3 promotes angiogenesis and sorafenib resistance in hepatocellular carcinoma via upregulating exosomal miR-494-3p.
Golgi phosphoprotein 3 promotes angiogenesis and sorafenib resistance in hepatocellular carcinoma via upregulating exosomal miR-494-3p.
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高尔基体磷蛋白3通过上调外泌体miR-494-3p促进肝细胞癌的血管生成和索拉非尼耐药
DOI：
10.1186/s12935-022-02462-9
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发表时间：
2022-01-24
影响因子：
5.8
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Gao Y;Yin Z;Qi Y;Peng H;Ma W;Wang R;Li W
高尔基体磷蛋白3（Golgi phosphoprotein 3，GOLPH 3）是一种常见的肿瘤蛋白。然而，其在癌症相关的细胞间信号传导中的作用尚未被探索。本研究旨在探讨GOLPH 3是否通过外泌体机制调节肝细胞癌（HCC）的血管生成和索拉非尼耐药。进行体内测定以阐明GOLPH 3在HCC中的功能。通过差速离心分离HCC细胞的外泌体，然后使用纳米颗粒跟踪分析（NTA）、BCA测定、蛋白质印迹（WB）和透射电子显微镜（TEM）测量和定量。通过小RNA测序（sRNA-seq）和逆转录聚合酶链反应（RT-PCR）分析和验证外泌体中差异表达的miRNA。此外，进行了一系列体外测定以确定外泌体和miR-494- 3 p在HCC中的功能。通过生物信息学预测和双荧光素酶报告基因分析，确定miR-494- 3 p的候选靶基因。GOLPH 3表达下调可抑制HCC中血管生成并增强索拉非尼敏感性。来源于GOLPH 3过表达的HCC细胞的外泌体促进HUVECs的血管生成能力并诱导HCC细胞中的索拉非尼抗性。在阴性对照组和GOLPH 3敲低组之间共发现13个差异表达的miRNAs。然而，GOLPH 3仅与来源于HCC细胞的外来体中的miR-494- 3 p表达水平相关，而不影响总细胞miR-494- 3 p含量。结果证实，外泌体miR-494- 3 p通过直接靶向PTEN促进HUVECs的血管生成和HCC细胞中的索拉非尼抗性。GOLPH 3高表达的HCC细胞可通过分别增强外泌体miR-494- 3 p向受体HUVECs和HCC细胞的分泌来促进血管生成和索拉非尼抗性。
Golgi phosphoprotein 3 (GOLPH3) has been frequently reported as an oncoprotein in a variety of tumors. However, its role in the cancer-associated intercellular signaling communication has not yet been explored. This study aimed at exploring whether GOLPH3 regulates angiogenesis and sorafenib resistance via exosomal mechanisms in hepatocellular carcinoma (HCC). In vivo assays were performed to elucidate the function of GOLPH3 in HCC. Exosomes of HCC cells were isolated by differential centrifugation, and then measured and quantified using nanoparticle tracking analysis (NTA), BCA assay, western blot (WB), and transmission electron microscopy (TEM). Differentially expressed miRNAs in exosome were analyzed and verified through small RNA sequencing (sRNA-seq) and reverse-transcription polymerase chain reaction (RT-PCR). In addition, a series of in vitro assays were performed to determine the function of exosomes and miR-494-3p in HCC. The candidate target gene of miR-494-3p was identified by bioinformatics prediction and dual-luciferase reporter assay. Downregulation of GOLPH3 expression could suppress angiogenesis and enhance sorafenib sensitivity in HCC. Exosomes derived from GOLPH3 overexpression HCC cells promoted the angiogenesis ability of HUVECs and induced sorafenib resistance in HCC cells. A total of 13 differentially expressed miRNAs between negative control and GOLPH3 knockdown group were found in exosomes. However, GOLPH3 was only associated with miR-494-3p expression level in exosomes derived from HCC cells without affecting total cellular miR-494-3p content. Results confirmed that exosomal miR-494-3p promotes angiogenesis of HUVECs and sorafenib resistance in HCC cells through directly targeting PTEN. HCC cells with high expression levels of GOLPH3 could promote angiogenesis and sorafenib resistance by enhancing exosomal miR-494-3p secretion to recipient HUVECs and HCC cells, respectively.
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影响因子：
11.1
作者：
Bernardi, Rosa;Papa, Antonella;Egia, Ainara;Coltella, Nadia;Teruya-Feldstein, Julie;Signoretti, Sabina;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
DOI：
10.12659/msm.893745
发表时间：
2015-08-18
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Bi D;Yang M;Zhao X;Huang S
通讯作者：
Huang S
影响因子：
--
作者：
Rontauroli S;Norfo R;Pennucci V;Zini R;Ruberti S;Bianchi E;Salati S;Prudente Z;Rossi C;Rosti V;Guglielmelli P;Barosi G;Vannucchi A;Tagliafico E;Manfredini R
通讯作者：
Manfredini R
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
高尔基体磷蛋白 3 (GOLPH3) 通过激活 NF-κB 通路促进肝细胞癌细胞侵袭性
影响因子：
7.3
作者：
Dai, Ting;Zhang, Dongsheng;Song, Libing
通讯作者：
Song, Libing