Abstract

Exosomes, nano-sized cell-derived vesicles, have been employed as non-synthetic carriers of various pharmaceutics in numerous studies. As higher expression levels of miR-142-3p and miR-150 in breast cancer stem cells (BCSCs) are associated with their clonogenic and tumorigenic capabilities, the present study aims to exploit the mesenchymal stem cells-derived exosomes (MSCs-Exo) to deliver LNA-antimiR-142-3p into MCF7-derived cancer stem-like cells to suppress expression levels of miR-142-3p and miR-150 in order to reduce clonogenicity and tumorigenicity. Our results indicated that the MSCs-Exo can efficiently deliver the LNA-antimiR-142-3p to breast cancer stem-like cells to reduce the miR-142-3p and miR-150 expression levels. Furthermore, the inhibition of the oncomiRs with the delivery of LNA-antimiR-142-3p resulted in a significant reduction of clone-formation and tumor-initiating abilities of the MCF7-derived cancer stem-like cells. In conclusion, we showed that MSCs-derived exosomes could be used as a feasible nanovehicles to deliver RNA-based therapeutics into BCSCs to improve the cancer treatment.

Highlights

• Exosomes secreted by bone marrow-derived mesenchymal stem cells efficiently transfer the LNA-antimiR-142-3p to breast cancer stem cells.
• Exosomes-mediated delivery of LNA-antimiR-142-3p to the breast cancer stem cells leads to downregulation of miR-142-3p and miR-150 and the overexpression of target genes.
• Delivery of LNA-antimiR-142-3p by the exosomes reduces the colony formation capability of breast cancer stem cells in vitro.
• Inhibition of miR-142-3p and miR-150 by the LNA-antimiR-142-3p loaded exosomes reduces the tumorigenicity of breast cancer stem cells in vivo.

中文翻译：

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间充质干细胞衍生的外来体将LNA-antimiR-142-3p递送至乳腺癌干细胞可降低致瘤性。

摘要

外来体，纳米级细胞衍生的囊泡，已在许多研究中用作各种药物的非合成载体。由于miR-142-3p和miR-150在乳腺癌干细胞（BCSC）中的较高表达水平与其克隆形成和致瘤能力有关，因此本研究旨在利用间充质干细胞衍生的外来体（MSCs-Exo）将LNA-antimiR-142-3p传递到MCF7衍生的癌症干细胞中，以抑制miR-142-3p和miR-150的表达水平，从而降低克隆形成性和致瘤性。我们的结果表明，MSCs-Exo可以有效地将LNA-antimiR-142-3p递送至乳腺癌干样细胞，从而降低miR-142-3p和miR-150的表达水平。此外，LNA-antimiR-142-3p的递送抑制了癌基因的表达，导致MCF7衍生的癌干样细胞的克隆形成和肿瘤启动能力显着降低。总之，我们表明，MSCs衍生的外泌体可以用作可行的纳米载体，以将基于RNA的治疗剂提供给BCSC，以改善癌症治疗。

强调

• 骨髓间充质干细胞分泌的外泌体可有效地将LNA-antimiR-142-3p转移至乳腺癌干细胞。
• 外来体介导的LNA-antimiR-142-3p向乳腺癌干细胞的递送导致miR-142-3p和miR-150的下调以及靶基因的过表达。
• 外泌体传递LNA-antimiR-142-3p会降低乳腺癌干细胞在体外的集落形成能力。
• 载有LNA-antimiR-142-3p的外来体抑制miR-142-3p和miR-150会降低体内乳腺癌干细胞的致瘤性。