Exosomes derived from cancer-associated fibroblasts promote tumorigenesis, metastasis and chemoresistance of colorectal cancer by upregulating circ_0067557 to target Lin28
Cheng Yang,
Yan Zhang,
Mingze Yan,
Jiahao Wang,
Jiaming Wang,
Muhong Wang,
Yuhong Xuan,
Haiyue Cheng,
Jiaao Ma,
Cuicui Chai,
Mingzhe Li,
Zhiwei Yu
Affiliations
Cheng Yang
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Yan Zhang
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Mingze Yan
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Jiahao Wang
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Jiaming Wang
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Muhong Wang
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Yuhong Xuan
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Haiyue Cheng
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Jiaao Ma
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Cuicui Chai
Digestive Disease Center, The Seventh Affiliated Hospital of Sun Yat-sen University
Mingzhe Li
Digestive Disease Center, The Seventh Affiliated Hospital of Sun Yat-sen University
Zhiwei Yu
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital
Abstract 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.
