Our study demonstrates that downregulation of hsa_circ_0007534 represses the proliferation and invasion of cervical cancer through regulating the miR-498/BMI-1 axis, suggesting the hsa_circ_0007534/miR-498/BMI-1 axis as a potential therapeutic target to treat cervical cancer.
These results suggest overexpression of miR-132 enhances the radiosensitivity of CC cells by down-regulating Bmi-1 and that miR-132 may be a useful new target for the treatment of CC.
Finally, tissue array studies demonstrated that expression of Bmi1 increased with the severity of cervical dysplasia, suggesting a potential role in the progression of cervical cancer.
Reverse transcription quantitative real-time PCR method was established to detect the circulating Bmi-1 mRNA in plasma of 109 patients with UCC, 138 patients with cervical intraepithelial neoplasia (CIN) and 80 healthy volunteers, and found that it was significantly increased in UCC compared with CINs and healthy controls (all at p < 0.001).
What's more, the levels of BMI-1 autoantibody increased significantly at stage I (0.672±0.019) compared to normal sera (P<0.001), and levels of BMI-1 autoantibodies were increased gradually during the tumor progression (stage I 0.672±0.019; stage II 0.775 ±0.019; stage III 0.890 ±0.027; stage IV 1.043±0.041), which were significantly correlated with disease progression of cervical cancer (P<0.001).
Moreover, immunohistochemical staining revealed Bmi-1 was overexpressed in 63.2% UCC tissues (Bmi-1 ++ or +++), and the overexpression of Bmi-1 protein was significantly correlated with tumor size (P = 0.046), clinical stage (P = 0.021), and regional lymph nodes metastasis (P = 0.010).