Abstract
Studies have shown that cancer-associated fibroblasts (CAFs) play an irreplaceable role in the occurrence and development of tumors. Therefore, exploring the action and mechanism of CAFs on tumor cells is particularly important. In this study, we compared the effects of CAFs-derived exosomes and normal fibroblasts (NFs)-derived exosomes on breast cancer cells migration and invasion. The results showed that exosomes from both CAFs and NFs could enter into breast cancer cells and CAFs-derived exosomes had a more enhancing effect on breast cancer cells migration and invasion than NFs-derived exosomes. Furthermore, microRNA (miR)-18b was upregulated in CAFs-derived exosomes, and CAFs-derived exosomes miR-18b can promote breast cancer cell migration and metastasis by specifically binding to the 3′UTR of Transcription Elongation Factor A Like 7 (TCEAL7). The miR-18b-TCEAL7 pathway promotes nuclear Snail ectopic activation by activating nuclear factor-kappa B (NF-κB), thereby inducing epithelial-mesenchymal transition (EMT) and promoting cell invasion and metastasis. Moreover, CAFs-derived exosomes miR-18b could promote mouse xenograft model tumor metastasis. Overall, our findings suggest that CAFs-derived exosomes miR-18b promote nuclear Snail ectopic by targeting TCEAL7 to activate the NF-κB pathway, thereby inducing EMT, invasion, and metastasis of breast cancer. Targeting CAFs-derived exosome miR-18b may be a potential treatment option to overcome breast cancer progression.
Highlights
Breast cancer is one of the common malignant tumors among women worldwide
Our findings suggest that cancer-associated fibroblasts (CAFs)-derived exosomes miR-18b promote nuclear Snail ectopic by targeting Transcription Elongation Factor A Like 7 (TCEAL7) to activate the normal fibroblasts (NFs)-κB pathway, thereby inducing epithelialmesenchymal transition (EMT), invasion, and metastasis of breast cancer
The results showed that fused in sarcoma (FUS), aconitase 1 (ACO1), and YTH domain containing 1 (YTHDC1) motifs have specific miR-18b binding sites (Fig. 3D)
Summary
Breast cancer is one of the common malignant tumors among women worldwide. Recurrence and metastasis are the main causes of death in breast cancer patients [1], and the tumor microenvironment has a more significant impact on the development and metastasis of tumors. RNAs of about 20 nucleotides in length They can bind to post-transcriptional mRNA to regulate gene expression leading to degradation of target genes or inhibition of protein expression [11]. The detailed role of CAF-derived exosomes carrying miR-18b in breast cancer remains unclear. TCEAL7 is downregulated in multiple tumors and functions as a tumor suppressor [21], such as non-small cell lung cancer [22]. The detailed role of TCEAL7 has not been thoroughly clarified in breast cancer. We found that TCEAL7 is negatively regulated by And after three times of elution with TBST, the secondary antibody linked miR-18b, in vivo, and in vitro experiments have demonstrated that exosomal miR-18b can promote the migration and invasion of breast cancer cells by targeting the expression of TCEAL7.
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