Hsa_circ_0000515 is a novel circular RNA implicated in the development of breast cancer through its regulation of the microRNA‐296‐5p/CXCL10 axis

Abstract

Cancer metastasis is a major cause of death among women afflicted with breast cancer (BC) and understanding the molecular processes involved is a major focus in BC research. Circular RNAs (circRNAs) have emerged as genomic regulatory molecules in carcinogenesis and metastasis; however, their role in BC is unclear. We characterized a novel circRNA, hsa_circ_0000515, in context of BC. We collected 340 cancerous tissues surgically resected from BC patients and found hsa_circ_0000515 was upregulated in BC tissues and associated with poor prognosis of BC. Silencing of hsa_circ_0000515 impaired cell cycle progression, cell proliferation, and invasion, attenuated inflammatory response, and reduced the proangiogenetic potential of BC cells. RNA pull‐down and dual‐luciferase reporter gene assays showed that hsa_circ_0000515 binds miR‐296‐5p, preventing it from repressing CXCL10 expression. We also observed that miR‐296‐5p inhibition or CXCL10 overexpression promoted cell cycle progression, restored proliferative, invasive and proangiogenetic abilities, and increased inflammatory response in MCF‐7 cells in the absence of hsa_circ_0000515. In vivo analyses showed that partial loss of hsa_circ_0000515 reduced the tumor growth of MCF‐7 cells in nude mice. The key findings from this study revealed that targeting hsa_circ_0000515 might be an effective strategy to combat BC.

Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer

“…Clinically, increased circCDYL in the BC tissues and serum was related to higher tumor burden, shorter survival, and poorer clinical response to treatment (Liang et al, 2020). Cai et al (2020) gathered in 340 BC tissues and identified hsa_circ_0000515 which was overexpressed and related to the poor prognosis of BC. Knockdown of hsa_circ_0000515 disrupted cell cycle progression, cell proliferation, and invasion, weakened inflammatory response, and decreased the proangiogenetic potential of BC cells (Cai et al, 2020).…”

“…Cai et al (2020) gathered in 340 BC tissues and identified hsa_circ_0000515 which was overexpressed and related to the poor prognosis of BC. Knockdown of hsa_circ_0000515 disrupted cell cycle progression, cell proliferation, and invasion, weakened inflammatory response, and decreased the proangiogenetic potential of BC cells (Cai et al, 2020). Regarding the mechanism, hsa_circ_0000515 could sponge miR-296-5p to hinder it from inhibiting CXCL10 expression.…”

The Biogenesis and Functions of circRNAs and Their Roles in Breast Cancer

“…( 88 ) confirmed through experiments that the downregulation of hsa_circRNA_002178 can inhibit aggressive malignant behaviors such as angiogenesis. At the same time, some scholars found that hsa_circ_0000515 and miR-296-5p modulated BC cell angiogenesis stimulated by CXCL10 specifically ( 89 ).…”

The Regulation Network and Clinical Significance of Circular RNAs in Breast Cancer

“…Circ-ABCB10 and circHMCU can sponge let-7 then regulate the expression of MCY, HMGA2, CCND1, and DUSP7, respectively, to promote the proliferation, invasion, migration, and chemoresistance of breast cancer cells (79,80). CircPLK1 and hsa_circ_0000515 can target miR-296-5p to regulate the expression of PLK1 and CXCL10, respectively, to promote the growth, proliferation, migration and inflammatory response of breast cancer cells (81,82). And surprisingly, hsa_circ_0011946 can interact with miR-26a/b to regulate RFC3, to promote the invasion and migration of breast cancer cells, whereas circWWC3 can interact with miR-26b-3p and miR-660-3p to regulate the expression of ZEB1, and thus promote the proliferation, invasion and migration of breast cancer cells (51,83).…”