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

circ_002172 的促癌作用与通过 miR-296-5p/CXCL12 轴诱导乳腺癌免疫逃逸有关

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作者:Pengfei Li, Xiangshun Ren, Yuanyuan Zheng, Jinming Sun, Gang Ye

Abstract

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.

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