CircZNF609 promotes breast cancer cell growth, migration, and invasion by elevating p70S6K1 via sponging miR-145-5p

Cancer Manag Res. 2018 Sep 25:10:3881-3890. doi: 10.2147/CMAR.S174778. eCollection 2018.

Abstract

Background: Accumulating evidence suggests that circular RNAs (circRNAs) play critical roles in carcinomas. However, the contributions of circRNAs to breast cancer remain unclear. Herein, we determined the role of circZNF609 in breast cancer.

Methods: A total of 143 breast cancer and 38 normal tissues were collected to assess the expression of circZNF609 and its relationship with breast cancer prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circZNF609 in breast cancer progression and its underlying molecular mechanisms.

Results: CircZNF609 was markedly over-expressed in breast cancer tissues and cell lines, and high circZNF609 expression was closely associated with poor outcome. Silencing of circZNF609 inhibited the malignant phenotype of breast cancer in vitro and in vivo. Mechanistically, circ-ZNF609 served as a sponge of miR-145-5p to elevate p70S6K1 expression. Moreover, miR-145-5p overexpression or p70S6K1 knockdown abrogated the oncogenic effects of circZNF609 in breast cancer. In addition, clinically, a strong negative correlation was observed between the expression of circZNF609 and miR-145-5p in breast cancer tissues (r=-0.597, P<0.001), whereas a positive correlation between circZNF609 and p70S6K1 expression (r=0.319, P<0.001).

Conclusion: These data suggest that circZNF609 contributes to breast cancer progression, at least partly, by modulating the miR-145-5p/p70S6K1 axis, and it may be a potential therapeutic target for breast cancer.

Keywords: CircRNAs; breast cancer; miRNA sponge; prognosis; progression.