Exosomes derived from cancer-associated fibroblasts promote tumorigenesis, metastasis and chemoresistance of colorectal cancer by upregulating circ_0067557 to target Lin28

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2024年1月12日

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Cheng Yang,
Yan Zhang,
Mingze Yan,
Jiahao Wang,
Jiaming Wang,
Muhong Wang,
Yuhong Xuan,
Haiyue Cheng,
Jiaao Ma,
Cuicui Chai,
Mingzhe Li,
Zhiwei Yu

摘要

Background

Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression.

Methods

Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay.

Results

Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors.

Conclusion

Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.