hnRNPA2B1-Mediated Extracellular Vesicles Sorting of miR-122-5p Potentially Promotes Lung Cancer Progression.

hnRNPA2B1-Mediated Extracellular Vesicles Sorting of miR-122-5p Potentially Promotes Lung Cancer Progression.
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hnRNPA2B1 介导的 miR-122-5p 细胞外囊泡分选可能促进肺癌进展

DOI:
10.3390/ijms222312866
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发表时间:
2021-11-28
影响因子:
5.6
通讯作者:
Sun G
Sun G
中科院分区:
生物学2区
文献类型:
--
作者:
Li C;Qin F;Wang W;Ni Y;Gao M;Guo M;Sun G

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肿瘤细胞释放的细胞外囊泡(EV)在重塑肿瘤间质环境和促进肿瘤转移方面发挥着重要作用。我们早期的研究表明,miR-122-5p(一种小非编码RNA)在非小细胞肺癌(NSCLC)细胞来源的EV中失调。在这项研究中,我们发现miR-122-5p通过与RNA结合蛋白hnRNPA2B1结合被选择性分选并分泌到肺癌EV中。此外,我们发现 hnRNPA2B1 通过 EXO 基序与 miR-122-5p 相互作用。肺癌EVs-miR-122-5p的递送促进了肝细胞的迁移,这可能在肺癌转移前微环境的建立和肝转移中发挥作用。重要的是,我们的研究结果揭示了RNA结合蛋白控制肿瘤来源的EV miR-122-5p选择性分选的分子机制,这可能促进肺癌进展。
Extracellular vesicles (EVs) released by tumor cells play important roles on the remodeling of the tumor–stromal environment and on promoting tumor metastasis. Our earlier studies revealed that miR-122-5p, a type of small non-coding RNA, was dysregulated in non-small cell lung cancer (NSCLC) cell-derived EVs. In this study, we found that miR-122-5p was selectively sorted and secreted into lung cancer EVs through binding to RNA-binding protein hnRNPA2B1. In addition, we found that hnRNPA2B1 interacted with miR-122-5p through the EXO-motif. The delivering of lung cancer EVs-miR-122-5p promoted the migration of liver cells, which may play roles in establishing a pre-metastatic micro-environment and hepatic metastasis of lung cancer. Importantly, our findings revealed the molecular mechanism that RNA-binding protein controls the selective sorting of tumor-derived EV miR-122-5p, which potentially promotes lung cancer progression.