Abstract
Background: Circular RNAs (circRNAs), covalently closed single-stranded non-coding RNAs (ncRNAs), play pivotal roles in development and progression of breast cancer (BC). Although the roles of hsa_circ_0013958 and hsa_circ_0003028 in some malignancies have been explored, their function and expression in breast tumors are still unknown. This study was aimed to bioinformatically and experimentally evaluates the expression and potential function of hsa_circ_0013958 and hsa_circ_0003028 in BC. Materials and Methods: The quantitative real-time PCR method was used to determine the expression of hsa_circ_0013958 and hsa_circ_0003028 in 50 tumor samples and matched adjacent non-cancerous tissues. Besides, we used bioinformatic approaches to identify potentially important competing endogenous RNA (ceRNA) networks that are regulated by these circRNAs using some databases and software tools. Results: The hsa_circ_0013958 was significantly down-regulated in breast tumors compared with adjacent normal tissues, while the hsa_circ_0003028 had an upregulated pattern. Interestingly, it is found the higher expression of hsa_circ_0013958 showed association with a lack of use of hair dye as well as age at menarche ≥14 years in subjects. On the other hand, hsa_circ_0003028 expression was meaningfully related to age at first full-term pregnancy, antiperspirants use, and regular menstruation. Next, we found that these two circRNAs can potentially regulate some circRNAs-mediated miRNA sponge regulatory networks. Conclusion: The current work indicated that the hsa_circ_0013958 and hsa_circ_0003028 had reverse expression patterns in breast tumors, and it seems that they play key roles in the physiopathology of this cancer through potential key regulatory ceRNA functions. However, further functional studies are needed to validate these bioinformatically observed roles. [GMJ.2021;10:e2064]
Highlights
Breast cancer (BC), a frequent malignant tumor, emerges as the secondary highest mortality among all tumors in women worldwide [1]
Transcription factor products of the mRNA member of the evaluated circRNA/miRNA/ mRNA networks We found that the mRNAs with having the transcription factor role involved in the predicted regulatory hsa_circ_0013958/miRNA/ mRNA network were SNAI2 and SP7
There is clear evidence that these mRNAs and miRNAs play key roles in the physiopathology of breast cancer (BC) [23,24,25,26,27]. Such observations point to the role of hsa_circ_0013958 in BC and the tumor-related function of this circRNA in BC may be the opposite of its roles which has been observed in these cancers
Summary
Breast cancer (BC), a frequent malignant tumor, emerges as the secondary highest mortality among all tumors in women worldwide [1]. Circular RNAs (circRNAs), covalently closed single-stranded non-coding RNAs (ncRNAs), play pivotal roles in development and progression of breast cancer (BC). Results: The hsa_circ_0013958 was significantly down-regulated in breast tumors compared with adjacent normal tissues, while the hsa_circ_0003028 had an upregulated pattern. It is found the higher expression of hsa_circ_0013958 showed association with a lack of use of hair dye as well as age at menarche ≥14 years in subjects. Conclusion: The current work indicated that the hsa_circ_0013958 and hsa_circ_0003028 had reverse expression patterns in breast tumors, and it seems that they play key roles in the physiopathology of this cancer through potential key regulatory ceRNA functions. Further functional studies are needed to validate these bioinformatically observed roles. [GMJ.2021;10:e2064]
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