CircRASSF2 acts as a prognostic factor and promotes breast cancer progression by modulating miR-1205/HOXA1 axis

Circular RNA (circRNA), a recently identified endogenous non-coding RNA molecule, regulates gene expression in mammals. At the current stage, the expression and function of circRASSF2 in breast cancer (BC) have not been clarified. According to our study, it is found that circRASSF2 sequences contain miR-1205 binding sites, and Homeobox gene A1 (HOXA1) is the target gene of miR-1205. Besides, the clinical observations and histopathologic study reveal that the expression of circRASSF2 increased to a significant extent in BC tissues and serum. Additionally, it is found that circRASSF2 expression had a positive correlation with distant metastasis, lymph node metastasis, TNM stage, differentiation and tumor size, and that overall survival (OS) and progression-free survival (PFS) of circRASSF2 high expression BC patients were inferior to those with low circRASSF2 expression. In vitro study, an overt decrease was detected in the proliferation, clone formation ability, migration and invasion of breast cancer cells in cells when circRASSF2 was knocked down. We confirmed the direct interaction between circRASSF2, miR-1205 and HOXA1 by a dual luciferase reporter system. Additionally, our study revealed that over-expression of miR-1205 decreased HOXA1 protein expression, and HOXA1 protein expression decreased when circRASSF2 were knocked down, and when miR-1205 expression was inhibited, HOXA1 expression was significantly increased. In conclusion, our study suggests that circRASSF2 regulates BC progression through the miR-1205/HOXA1 pathway. Our findings suggest the prospect of circRASSF2 serving as therapeutic target as such to cure BC patients.

Automated summary

Our study revealed that circRASSF2 regulates BC progression through the miR-1205/HOXA1 pathway. High expression of circRASSF2 is associated with distant metastasis, lymph node metastasis, TNM stage, differentiation, and tumor size in BC patients, leading to inferior overall survival (OS) and progression-free survival (PFS). This indicates the potential of circRASSF2 as a therapeutic target for treating BC patients.