School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Int J Mol Sci. 2021 Nov 28;22(23):12866. doi: 10.3390/ijms222312866.
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.
肿瘤细胞释放的细胞外囊泡（EVs）在重塑肿瘤基质环境和促进肿瘤转移方面发挥着重要作用。我们之前的研究表明，微小 RNA-122-5p（一种小的非编码 RNA）在非小细胞肺癌（NSCLC）细胞衍生的 EVs 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，被选择性地分拣并分泌到肺癌 EVs 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 的递呈促进了肝细胞的迁移，这可能在建立前转移微环境和肺癌肝转移中发挥作用。重要的是，我们的研究结果揭示了 RNA 结合蛋白控制肿瘤衍生 EV miR-122-5p 的选择性分拣的分子机制，这可能促进了肺癌的进展。
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