Knockdown of circ_0102273 inhibits the proliferation, metastasis and glycolysis of breast cancer through miR-1236-3p/PFKFB3 axis

Abstract

The key regulatory roles of circular RNAs (circRNAs) in human diseases have been demonstrated, including breast cancer (BC). The purpose of this study is to explore the role of circ_0102273, a newly discovered circRNA, in BC progression. The expression levels of circ_0102273, microRNA (miR)-1236-3p and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) were determined by quantitative real-time PCR. Cell proliferation, migration and invasion were measured using colony formation assay, EdU staining, wound healing assay and transwell assay. Glucose consumption, lactate production and ATP level were detected to evaluate cell glycolysis. The interaction between miR-1236-3p and circ_0102273 or PFKFB3 was confirmed by dual-luciferase reporter assay and RIP assay. Additionally, western blot analysis was utilized for measuring PFKFB3 protein expression. In-vivo experiments were performed to further explore the function of circ_0102273 in BC tumorigenesis. Our data showed that circ_0102273 was highly expressed in BC tumor tissues and cells, and its downregulation could inhibit BC cell proliferation, metastasis and glycolysis. MiR-1236-3p was confirmed to be sponged by circ_0102273, and its inhibitor could reverse the negative regulation of sh-circ_0102273 on BC cell proliferation, metastasis and glycolysis. PFKFB3 could be targeted by miR-1236-3p, and its expression could be positively regulated by circ_0102273. In addition, miR-1236-3p could suppress BC cell proliferation, metastasis and glycolysis, while this effect could be abolished by PFKFB3. Furthermore, circ_0102273 knockdown also had been discovered to reduce BC tumorigenesis in vivo. In summary, our research proposed that circ_0102273 might be a potential target for BC treatment, which could inhibit BC proliferation, metastasis and glycolysis through the miR-1236-3p/PFKFB3 axis.

Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications

“…The intracellular steady-state concentration of F-2,6-BP is controlled by the homodimeric bifunctional enzyme PFK-2/FBPase (PFKFB)family [ 59 ]. Research has shown that circ_0102273 could upregulate PFKFB3 expression by sponging miR-1236-3p , which, in turn, promoted breast cancer proliferation, metastasis, and glycolysis [ 60 ]. Wang et al found that PFKFB3 was a direct target of tRiMetF31 , and knockdown of tRiMetF31 restored PFKFB3-driven angiogenesis, with elevated PFKFB3 significantly correlating with metastasis [ 61 ].…”

Senescent cells develop PDK4-dependent hypercatabolism and form an acidic microenvironment to drive cancer resistance

“…4a). Multiple studies reported that cancer cells have increased lactate production, OCR level and ATP production, a series of metabolic changes correlated with enhanced glycolysis (Yu et al, 2022;. Strikingly, we found that many relevant activities of senescent cells were even higher than those of cancer cells selected as of the same organ origin (herein, prostate), such as PC3 and DU145, although with several key features manifesting changes evidently opposite to those of examined cancer lines (Supplementary Fig.…”

Senescent cells develop PDK4-dependent hypercatabolism and form an acidic microenvironment to drive cancer resistance

“…4a). Multiple studies reported that cancer cells have increased lactate production, OCR level and ATP production, a series of metabolic changes correlated with enhanced glycolysis 34, 35 . Strikingly, we found that many relevant activities of senescent cells were even higher than those of cancer cells selected as of the same organ origin (herein, prostate), such as PC3 and DU145, although with several key features manifesting changes evidently opposite to those of examined cancer lines (Supplementary Fig.…”