Breast cancer-derived exosomal lncRNA SNHG14 induces normal fibroblast activation to cancer-associated fibroblasts via the EBF1/FAM171A1 axis
Huaying Dong, Changcheng Yang, Xiang Chen, Hening Sun, Xionghui He, Wei Wang
Abstract
BACKGROUND: Exosomes released from cancer cells can activate normal fibroblasts (NFs) into cancer-associated fibroblasts (CAFs), which promotes cancer development. Our study aims to explore the role and potential mechanisms of breast cancer exosomes-delivered long non-coding RNA (lncRNA) SNHG14 in regulating CAFs transformation. METHODS: Adjacent normal tissues, cancerous and serum specimens were gathered in breast cancer patients. Exosomes and NFs were separated from breast cancer cells (SKBR-3) and normal tissues of patients, respectively. Cell viability and migration were measured with CCK-8 and Transwell assays. CAFs markers, fibroblast activation protein (FAP) and a-smooth muscle actin (α-SMA) were detected for assessing CAFs activation. The interactions between molecules were evaluated using dual luciferase reporter assay, RNA immunoprecipitation and chromatin immunoprecipitation. RESULTS: SNHG14 and FAM171A1 were upregulated in breast cancer. Exosomes secreted by SKBR-3 cells induced NFs activation in CAFs, as indicated by upregulating CAFs marker levels and facilitated cell viability and migration. Exosomal SNHG14 silencing in SKBR-3 cells inhibited CAFs activation. SNHG14 positively regulated FAM171A1 expression through EBF1. FAM171A1 overexpression eliminated the inhibition effect of exosomal SNHG14 silencing in CAFs transformation. CONCLUSION: Breast cancer-derived exosomal SNHG14 contributed to NFs transformation into CAFs by the EBF1/FAM171A1 axis.