Abstract
BackgroundBreast cancer (BC) is the most commonly malignant tumor among women worldwide. Many studies have reported that circular RNAs (circRNAs) were participated in the regulation of multiple cancers development. However, the mechanism underlying hsa_circ_0001982 in breast cancer development is still unclear.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001982, microRNA-1287-5p (miR-1287-5p), and mucin 19 (MUC19) in BC tissues and cells under hypoxia. Moreover, glycolysis was evaluated by glucose consumption, lactic acid production, and hexokinase II (HK2) protein levels. The protein levels of cyclin D1, proliferating cell nuclear antigen (PCNA), and HK2 were determined by western blot assay. Cell proliferation, migration, and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (MTT) and transwell assays, respectively. The relationship between miR-1287-5p and circ_0001982 or MUC19 was predicted using starbase v3.0 or Targetscan, and verified by dual-luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. The xenograft model in nude mice was established to examine the effect of circ_0001982 in vivo.ResultsThe levels of circ_0001982 and MUC19 were upregulated, while miR-1287-5p was downregulated in BC tissues and cells under hypoxia. Knockdown of circ_0001982 hindered glycolysis, cell viability, migration, and invasion of BC cells under hypoxia. Mechanistic studies discovered that circ_0001982 could act as a sponge for miR-1287-5p to enhance MUC19 expression in BC cells. In addition, circ_0001982 silencing reduced xenograft tumor growth by regulating miR-1287-5p/MUC19 axis.ConclusionCirc_0001982 affected BC cells glycolysis, proliferation, migration, and invasion through miR-1287-5p/MUC19 axis under hypoxia.
Highlights
The epidemiological investigation shows that cancer caused vast numbers of deaths in women [1, 2]
We explored the pivotal molecule mechanism underlying the regulation of glucose consumption, lactate production and Hexokinase 2 (HK2) expression in Breast cancer (BC) cells
Tissue samples BC tissues and adjacent normal tissues were obtained from 35 BC patients, who were recruited from Jiangxi Cancer Hospital, and stored at – 80 °C immediately
Summary
The epidemiological investigation shows that cancer caused vast numbers of deaths in women [1, 2]. Targeted therapy has significantly improved the survival rate of BC patients over the past 30 years, providing a new thinking for BC therapy [5]. Deep understanding of the molecular mechanism underlying BC progression is essential for developing targeted therapy. To enhance survival in a hypoxia environment, cancer cells undergo a socalled metabolic transformation, which with the hallmarks of the enhanced glycolysis and reduced oxidative phosphorylation, termed the Warburg effect [7]. We explored the pivotal molecule mechanism underlying the regulation of glucose consumption, lactate production and HK2 expression in BC cells. Breast cancer (BC) is the most commonly malignant tumor among women worldwide. Many studies have reported that circular RNAs (circRNAs) were participated in the regulation of multiple cancers development. The mechanism underlying hsa_circ_0001982 in breast cancer development is still unclear
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