Exosome‐transported circ_0001955 as a potent driver of breast cancer by regulating the miR‐708‐5p/PGK1 axis

Abstract

Abstract Background Increasing evidence shows that exosome‐mediated delivery of circular RNA (circRNA) is implicated in breast cancer progression. This study aimed to elucidate the role of exosome‐transported circ_0001955 in breast cancer. Methods The expression of circ_0001955, miR‐708‐5p, and phosphoglycerate kinase 1 (PGK1) messenger RNA (mRNA) was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR); the protein levels of PGK1 and hexokinase 2 (HK2) were detected by western blot (WB). 5′‐Ethynyl‐2′‐deoxyuridine (EdU) and colony formation assay were used to determine cell proliferation. Glycolytic metabolism was analyzed by corresponding kits to detect the associated indicators. The role of circ_0001955 in vivo was studied by establishing animal models. The potential binding relationship between miR‐708‐5p and circ_0001955 or PGK1 was verified by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results Circ_0001955 was highly expressed in breast cancer tissues and cell lines, as well as in exosomes from breast cancer cell lines. The deficiency of circ_0001955 blocked proliferation, decreased the IC50 value of paclitaxel (PTX), and blocked glycolysis in MCF‐7 and MDA‐MB‐231 cells. Circ_0001955 knockdown also inhibited tumor growth in vivo. Circ_0001955 directly combined with miR‐708‐5p, and the miR‐708‐5p inhibitor reversed the effects of sh‐circ_0001955. PGK1 was a target of miR‐708‐5p, and circ_0001955 indirectly promoted PGK1 expression by binding to miR‐708‐5p. PGK1 overexpression abolished the function of miR‐708‐5p in breast cancer. Conclusion Exosomal circ_0001955 excreted from breast cancer cells facilitated proliferation and glycolysis and enhanced the IC50 value of PTX in breast cancer cells by sponging miR‐708‐5p to upregulate PGK1.

Keywords

• breast cancer
• circ_0001955
• exosome
• miR‐708‐5p
• PGK1