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Breast cancer-derived exosomal lncRNA SNHG14 induces normal fibroblast activation to cancer-associated fibroblasts via the EBF1/FAM171A1 axis

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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.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

lncRNAs:

Long non-coding RNAs

SNHG14:

Small nucleolar RNA host gene 14

NFs:

Normal fibroblasts

CAFs:

Cancer-associated fibroblasts

EBF1:

Early B cell factor 1

FAM171A1:

The family with sequence similarity 171, member A1 protein

α-SMA:

A-smooth muscle actin

FAP:

Fibroblast activation protein

TFF3:

Trefoil factor 3

KLF5:

Kruppel-like factor 5

LMTK3:

Lemur tyrosine kinase-3

EGR1:

Early growth response protein 1

KLF7:

Krüppel-like factor 7

CTSF:

Cathepsin F

HEY1:

YRPW motif 1

C16orf74:

Chromosome 16 open reading frame 74

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Acknowledgements

Not applicable.

Funding

This work was supported by The Key Research and Development Program of Hainan Province (ZDYF2021SHFZ055) and Hainan Provincial Natural Science Foundation of China (822CXTD535) and National Science Foundation of China (81960475).

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Author notes

  1. Huaying Dong and Changcheng Yang are the co-first authors.

Authors and Affiliations

  1. Department of General Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No 19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan Province, People’s Republic of China

    Huaying Dong, Xiang Chen, Hening Sun, Xionghui He & Wei Wang

  2. Department of Oncology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, Hainan Province, People’s Republic of China

    Changcheng Yang

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  1. Huaying Dong
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Correspondence to Wei Wang.

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Dong, H., Yang, C., Chen, X. et al. Breast cancer-derived exosomal lncRNA SNHG14 induces normal fibroblast activation to cancer-associated fibroblasts via the EBF1/FAM171A1 axis. Breast Cancer 30, 1028–1040 (2023). https://doi.org/10.1007/s12282-023-01496-9

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