Abstract

Background: There is increasing evidence that circular RNAs (circRNAs) participate in regulating cancer progression. However, the function and potential molecular mechanisms of circRNA in triple negative breast cancer (TNBC) are currently largely unclear.Results: We found that circAHNAK1 was significantly down-regulated in TNBC, and its expression was negatively associated with RFS and OS. Overexpression of circAHNAK1 can inhibit TNBC proliferation, migration and invasion in vitro. In vivo studies confirmed that circAHNAK1 inhibited TNBC tumor growth and metastasis. Mechanistic analysis indicated that circAHNAK1 acted as a miR-421 ceRNA (competitive endogenous RNA) to attenuate the inhibitory effect of miR-421 on its target gene RASA1.Conclusions: In conclusion, CircAHNAK1 inhibits proliferation and metastasis of TNBC by modulating miR-421 and RASA1.Methods: CircRNA microarrays were used to screen for differential circRNA expression profiles. qRT-PCR was used to detect the expression levels of circRNAs. The effect of circAHNAK1 on recurrence -free survival (RFS) and overall survival (OS) in patients with TNBC was subsequently analyzed. The role of circAHNKA1 in the progression of TNBC was further evaluated by multiple in vivo and in vitro assays. Finally, we focused on the regulation of circAHNAK1 on miR-421 and its targeted gene RASA1 in TNBC.

Highlights

  • Triple-negative breast cancer (TNBC) is one of the most deadly types of breast cancer

  • Our result suggested that circRNA is significantly down-regulated in stage III–IV triple negative breast cancer (TNBC) tissues compared to stage I–II (Supplementary Figure 1D)

  • We evaluated the function of circ-AHNAK1, which is a novel circRNA derived from the AHNAK locus

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Summary

Introduction

Triple-negative breast cancer (TNBC) is one of the most deadly types of breast cancer. Some endogenous non-coding RNAs such as circRNA are closely related to tumor cell proliferation, apoptosis and metastasis by regulating a large number of signaling pathways in cancer [4, 5]. The function and potential molecular mechanisms of circRNA in triple negative breast cancer (TNBC) are currently largely unclear. Results: We found that circAHNAK1 was significantly down-regulated in TNBC, and its expression was negatively associated with RFS and OS. Conclusions: In conclusion, CircAHNAK1 inhibits proliferation and metastasis of TNBC by modulating miR-421 and RASA1. QRT-PCR was used to detect the expression levels of circRNAs. The effect of circAHNAK1 on recurrence -free survival (RFS) and overall survival (OS) in patients with TNBC was subsequently analyzed. We focused on the regulation of circAHNAK1 on miR-421 and its targeted gene RASA1 in TNBC

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