Exosomal miR-590-3p derived from cancer-associated fibroblasts confers radioresistance in colorectal cancer.
Exosomal miR-590-3p derived from cancer-associated fibroblasts confers radioresistance in colorectal cancer.
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源自癌症相关成纤维细胞的外泌体 miR-590-3p 赋予结直肠癌放射抗性。
DOI：
10.1016/j.omtn.2020.11.003
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发表时间：
2021-06-04
期刊：
影响因子：
--
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Chen X;Liu Y;Zhang Q;Liu B;Cheng Y;Zhang Y;Sun Y;Liu J
辐射抗性是结直肠癌（CRC）有效治疗的主要障碍。microRNAs（miRNAs）在化疗抗性和辐射抗性中起关键作用。本研究旨在探讨miR-590- 3 p是否参与大肠癌的放射抵抗。miR-590- 3 p在结直肠癌组织和细胞系中均呈高表达，而CLCA 4呈低表达。CLCA 4是miR-590- 3 p的靶基因。提取CAF衍生的外泌体并与CRC细胞共培养，然后将其暴露于辐射。用质粒转染CRC细胞并注射到裸鼠中以检测CAF衍生的外泌体的体内作用。用CAF衍生的外泌体处理降低了CRC细胞对辐射的敏感性。过表达miR-590- 3 p的CAF衍生的外泌体增加细胞存活率和p-PI 3 K/PI 3 K和p-AKT/AKT的比率，同时降低细胞中切割的PARP、切割的caspase 3和γ H2 AX的表达。此外，体内实验结果证实，CAF衍生的外泌体miR-590- 3 p在放射治疗后刺激小鼠中的肿瘤生长。我们的研究结果表明，miR-590- 3 p通过来自CAF的外泌体递送，通过CLCA 4依赖性PI 3 K/Akt信号通路的正调控增强CRC的放射抗性。miR-590- 3 p在结直肠癌组织和细胞系中均呈高表达，而CLCA 4呈低表达。用CAF衍生的外泌体处理降低了CRC细胞对辐射的敏感性。通过源自CAF的外泌体递送miR-590- 3 p通过CLCA 4依赖性PI 3 K/Akt信号传导途径的正调节增强CRC中的辐射抗性。
Radiotherapeutic resistance is a major obstacle for the effective treatment of colorectal cancer (CRC). MicroRNAs (miRNAs) play a critical role in chemoresistance and radioresistance. Here, we aimed to investigate whether miR-590-3p participates in the radioresistance of CRC. High expression of miR-590-3p and low expression of CLCA4 were found in both CRC tissues and cell lines. CLCA4 was indicated to be a target gene of miR-590-3p. CAF-derived exosomes were extracted and co-cultured with CRC cells, which were then exposed to radiation. CRC cells were transfected with plasmids and injected into nude mice to detect the in vivo effect of CAF-derived exosomes. Treatment with CAF-derived exosomes decreased the sensitivity of CRC cells to radiation. CAF-derived exosomes overexpressing miR-590-3p increased cell survival and the ratio of p-PI3K/PI3K and p-AKT/AKT while lowering the expressions of cleaved-PARP, cleaved-caspase 3, and γH2AX in cells. Furthermore, in vivo experimental results confirmed that CAF-derived exosomal miR-590-3p stimulated tumor growth in mice following radiotherapy. Our results demonstrate that miR-590-3p delivery via exosomes derived from CAFs enhances radioresistance in CRC through the positive regulation of the CLCA4-dependent PI3K/Akt signaling pathway. High expression of miR-590-3p and low expression of CLCA4 were found in both CRC tissues and cell lines. Treatment with CAF-derived exosomes decreased the sensitivity of CRC cells to radiation. miR-590-3p delivery via exosomes derived from CAFs enhances radioresistance in CRC through the positive regulation of the CLCA4-dependent PI3K/Akt signaling pathway.
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DOI：
10.18632/aging.101355
发表时间：
2017-12-28
期刊：
Aging
影响因子：
--
作者：
Bhome R;Goh RW;Bullock MD;Pillar N;Thirdborough SM;Mellone M;Mirnezami R;Galea D;Veselkov K;Gu Q;Underwood TJ;Primrose JN;De Wever O;Shomron N;Sayan AE;Mirnezami AH
通讯作者：
Mirnezami AH
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影响因子：
12.3
作者：
Qin, Xing;Guo, Haiyan;Zhang, Jianjun
通讯作者：
Zhang, Jianjun
影响因子：
1.2
作者：
Dai, Guangyao;Yao, Xiaoguang;Zhang, Jingcheng
通讯作者：
Zhang, Jingcheng
梗塞心脏恶劣的微环境加速移植骨髓间充质干细胞损伤：受损心肌细胞来源的外泌体的作用
影响因子：
9
作者：
Hu M;Guo G;Huang Q;Cheng C;Xu R;Li A;Liu N;Liu S
通讯作者：
Liu S
影响因子：
11.5
作者：
Jin, Xiance;Chen, Yanfan;Xie, Congying
通讯作者：
Xie, Congying