Tumor promoting effect of circ_002172 associates with induced immune escape in breast cancer via the miR-296-5p/CXCL12 axis

Comprehending the biology of tumorigenesis needs identification of determinants of the immune reaction during cancer development. This study intends to illustrate the mechanistic actions of a bioinformatically predicted circRNA circ_002172 in cytotoxic T lymphocytes (CTL) infiltration and escape of breast cancer (BC) from immunological destruction. Expression patterns of circ_002172, miR-296-5p, and CXCL12 were determined in BC tissues and cells. Effects of circ_002172, miR-296-5p, and CXCL12 on cell viability, migration, and invasion were examined through artificial modulation of their expression. The role of circ_002172 and CXCL12 on tumorigenesis was validated in subcutaneously transplanted and orthotopically transplanted tumors in nude mice. Upregulation of circ_002172 and CXCL12 and downregulation of miR-296-5p occurred in BC tissues and cells. Circ_002172 promoted the oncogenic phenotypes of BC cells in vitro and growth of tumors in vivo, which was reversed by knockdown of CXCL12 expression. Circ_002172, as a miR-296-5p sponge, upregulated expression CXCL12. Moreover, Ectopic expression of circ_002172 inhibited cytotoxic T lymphocytes (CTL) infiltration to promote the immune escape of BC. In conclusion, the tumor-promoting role of circ_002172 in BC was achieved by inducing immune escape via the miR-296-5p/CXCL12 axis.