Abstract
Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.
Highlights
Breast cancer (BC) has become the top killer among malignant tumors in female all over the world [1]
The raw data were analyzed with R studio to screen differentially expressed Circular RNA (circRNA) in BC
Numerous of circRNAs have been proved to participate in the biogenesis and progression of multiple tumors including BC [17]
Summary
Breast cancer (BC) has become the top killer among malignant tumors in female all over the world [1]. Circular RNA (circRNA), a group of endogenous non-coding RNA, has shown its effect gradually on tumorigenesis, progression, recurrence, metastasis and drug resistance in recent years [5]. The functions and mechanisms are mainly related to the subcellular distributions of circRNAs. It has been reported that circRNAs located in cytoplasm act as translation templates or sponges of microRNAs (miRNAs) and proteins, while those in the nucleus can regulate the expression of genes [6]. Due to their single-stranded, covalently closed circular structures without 5′-caps or 3′-poly(A) tails, circRNAs are more resistant to degradation and more stable than linear transcripts [11]. This property makes it possible for circRNAs to become biomarkers for tumor diagnosis [12]
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