circAR-E2E4-miR-665-STAT3 axis is a potential regulatory network in triple-negative breast cancer

Hao Xu; Mengdie Fang; Bowen Zuo; Wanxin Yao; Juan Ren; Yanmei Zhang

doi:10.1016/j.heliyon.2022.e12654

circAR-E2E4-miR-665-STAT3 axis is a potential regulatory network in triple-negative breast cancer

Heliyon. 2022 Dec 23;9(1):e12654. doi: 10.1016/j.heliyon.2022.e12654. eCollection 2023 Jan.

Authors

Hao Xu^{1

2}, Mengdie Fang¹, Bowen Zuo¹, Wanxin Yao¹, Juan Ren¹, Yanmei Zhang¹

Affiliations

¹ School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 310013, China.
² Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China.

Abstract

Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs (ncRNA). Many studies showed that circRNAs played different biological functions in triple-negative breast cancer (TNBC). However, the potential molecular mechanism of circRNAs in TNBC still remains to be investigated. In this study, circAR-E2E4 was defined as a novel circRNA involved in TNBC progression, derived from and regulated by androgen receptor (AR). CCK-8 assay showed circAR-E2E4 regulated TNBC cell proliferation. Potential binding miRNAs of circAR-E2E4 were predicted and miR-665 was identified to have a great prognosis value. Three databases were employed to predict target genes of miR-665, and STAT3 was regarded as the most potential downstream genes analyzed by protein-protein interaction (PPI), hub gene screening, correlation analysis, and survival analysis. Finally, knockdown of circAR-E2E4 led to the decrease of STAT3 expression. Collectively, the regulatory network circAR-E2E4-miR-665-STAT3 axis we constructed was associated with TNBC progression, providing a promising diagnostic, prognostic, and therapeutic target in future treatment for TNBC.

Keywords: Androgen receptor; Circular RNA; STAT3; Triple-negative breast cancer; microRNA.