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Non-small cell lung cancer cell–derived exosomal miR-17-5p promotes osteoclast differentiation by targeting PTEN
Experimental Cell Research ( IF 3.7 ) Pub Date : 2021-09-16 , DOI: 10.1016/j.yexcr.2021.112834
Mengyan Wang 1 , Mingna Zhao 1 , Qiaomei Guo 1 , Jiatao Lou 2 , Lin Wang 2
Affiliation  

Aberrant activity of bone resorbing osteoclasts plays a key role in the development of osteoporosis and cancer bone metastasis. The identification of novel and specific targets will be helpful for the development of new therapeutic strategies for bone metastasis in lung cancer. Herein, we examined microRNAs in tumor cell-derived exosomes to investigate the communication between the bone environment and tumor cells. TCGA database analysis showed that the level of miR-17-5p increased in non-small cell lung cancer tissues compared with non-tumor tissues. To investigate the function of exosomes in inducing osteoclastogenesis, osteoclast precursors were incubated with exosomes isolated from non-small cell lung cancer cell line, as well as receptor activator of NF-KB ligand and M-CSF to induce osteoclastogenesis. We found that exosomal miR-17-5p is upregulated in a non-small cell lung cancer cell line with bone metastasis compared with the original cell line. Overexpression of miR-17-5p enhanced the osteoclastogenesis of RAW264.7 cells. PTEN was identified as a direct target of miR-17-5p and showed negative effects on osteoclastogenesis. Importantly, treatment of LY294002 (an inhibitor of the PI3K/Akt pathway) attenuated miR-17-5p-mediated osteoclastogenesis effects. Taken together, our findings demonstrated that miR-17-5p promotes osteoclastogenesis through the PI3K/Akt pathway via targeting PTEN in lung cancer.



中文翻译:

非小细胞肺癌细胞衍生的外泌体miR-17-5p通过靶向PTEN促进破骨细胞分化

骨吸收破骨细胞的异常活性在骨质疏松症和癌症骨转移的发展中起着关键作用。新的特异性靶点的鉴定将有助于开发肺癌骨转移的新治疗策略。在此,我们检查了肿瘤细胞来源的外泌体中的 microRNA,以研究骨环境与肿瘤细胞之间的通讯。TCGA数据库分析显示,与非肿瘤组织相比,非小细胞肺癌组织中miR-17-5p水平升高。为了研究外泌体在诱导破骨细胞生成中的功能,将破骨细胞前体与从非小细胞肺癌细胞系中分离的外泌体以及 NF-KB 配体和 M-CSF 的受体激活剂一起培养以诱导破骨细胞生成。我们发现与原始细胞系相比,外泌体 miR-17-5p 在具有骨转移的非小细胞肺癌细胞系中上调。miR-17-5p 的过表达增强了 RAW264.7 细胞的破骨细胞生成。PTEN 被确定为 miR-17-5p 的直接靶标,并对破骨细胞生成产生负面影响。重要的是,LY294002(PI3K/Akt 通路抑制剂)的治疗减弱了 miR-17-5p 介导的破骨细胞生成作用。总之,我们的研究结果表明,miR-17-5p 通过靶向肺癌中的 PTEN,通过 PI3K/Akt 途径促进破骨细胞生成。PTEN 被确定为 miR-17-5p 的直接靶标,并对破骨细胞生成产生负面影响。重要的是,LY294002(PI3K/Akt 通路抑制剂)的治疗减弱了 miR-17-5p 介导的破骨细胞生成作用。总之,我们的研究结果表明,miR-17-5p 通过靶向肺癌中的 PTEN,通过 PI3K/Akt 途径促进破骨细胞生成。PTEN 被确定为 miR-17-5p 的直接靶标,并对破骨细胞生成产生负面影响。重要的是,LY294002(PI3K/Akt 通路抑制剂)的治疗减弱了 miR-17-5p 介导的破骨细胞生成作用。总之,我们的研究结果表明,miR-17-5p 通过靶向肺癌中的 PTEN,通过 PI3K/Akt 途径促进破骨细胞生成。

更新日期:2021-09-27
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