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

ABSTRACT

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.

KEYWORDS:

• Breast cancer
• circRASSF2
• miR-1205
• proliferation
• migration
• invasion

Highlights

1. CircRASSF2 upregulation was correlated with the progression and poor prognosis in BC.

2. CircRASSF2 can be a good diagnosis marker for BC.

3. CircRASSF2 downregulation can inhibit BC cell proliferation and induce apoptosis.

4. CircRASSF2 downregulation can inhibit BC cell migration and invasion.

5. CircRASSF2 can up-regulate HOXA1 protein levels in BC cells via sponging miR-1205.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author contributions

Y Meng and W Zhong designed and performed the experiments. All authors wrote and approved the final manuscript.

Ethics statement

The study has obtained approval from the Research Medical Ethics Committee of Wuhan Youfu Hospital. The patients involved have submitted their written informed consent.