Altered Expression of hsa_circ_0001445 and hsa_circ_0020397 in Breast Cancer Representing Associations with BMI and Reproductive Factors

Background: Circular RNAs (circRNAs), one of the recent subclasses of non-coding RNAs (ncRNAs), show pivotal functions in regulation of gene expression and have significant roles in malignancies including breast cancer (BC). This study was aimed to assess the hsa_circ_0001445 and hsa_circ_0020397 expression and role in BC, as well as the potential circRNA/miRNA/mRNA crosstalk in these contexts.

Methods: The expression of hsa_circ_0001445 and hsa_circ_0020397 in 50 breast tumors and 50 normal tissues adjacent to the tumors was investigated using quantitative real-time polymerase chain reaction (qRT-PCR). Finally, bioinformatics analyses were used to uncover hsa_circ_0001445, hsa_circ_0020397-miRNA-mRNA potential regulatory networks.

Results: The hsa_circ_0001445 expression was considerably downregulated in malignant tissues compared to their normal counterparts (P=0.020), while the hsa_circ_0020397 showed an upregulated pattern (P<0.001). Additionally, it was observed that the higher expression of hsa_circ_0001445 was associated with hair dye avoidance (P=0.034) and normal body mass index (BMI) (P=0.016) while hsa_circ_0020397 over-expression had an important association with a lack of vitamin D consumption (P=0.039). On the other hand, lower expression of hsa_circ_0001445 was significantly associated with age at menarche ˂14 years (P=0.027). Our study also revealed that the two circRNAs have potential ability to regulate key mRNAs and miRNAs in competing endogenous RNA (ceRNA) networks.

Conclusion: It is suggested that hsa_circ_0001445 and hsa_circ_0020397 with two opposite roles may be involved in BC development through sponging some miRNAs regulating ceRNA networks. However, their molecular interactions should be validated by further functional studies.