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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
Author(s) -
Cai Fenglin,
Fu Wenjie,
Tang Lei,
Tang Jinhai,
Sun Jinming,
Fu Guangshun,
Ye Gang
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15373
Subject(s) - gene silencing , microrna , cancer research , carcinogenesis , circular rna , metastasis , context (archaeology) , cancer , cell growth , downregulation and upregulation , biology , tumor progression , in vivo , breast cancer , cell cycle , gene , genetics , paleontology
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.