<p>Circ-ZNF609 Accelerates the Radioresistance of Prostate Cancer Cells by Promoting the Glycolytic Metabolism Through miR-501-3p/HK2 Axis</p>

Abstract

Background: The development of radioresistance remains the obstacle for prostate cancer (PCa) treatment. Here, we explored the role and potential mechanism of circular RNA zinc finger protein 609 (circ-ZNF609) in the radioresistance of PCa cells. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ-ZNF609, microRNA-501-3p (miR-501-3p) and hexokinase 2 (HK2) messenger RNA (mRNA). The viability, apoptosis, metastasis and radioresistance of PCa cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, transwell assays and colony formation assay. The glycolytic rate was assessed through measuring the glucose consumption and lactate production using fluorescencebased glucose and lactate assay kits. The target interaction between miR-501-3p and circ-ZNF609 or HK2 was predicted by StarBase software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The protein level of HK2 was detected by Western blot assay. In vivo tumor growth assay was used to explore the role of circ-ZNF609 in the radioresistance of PCa in vivo. Results: Circ-ZNF609 was abnormally up-regulated in PCa tissues and cell lines. Circ-ZNF609 silencing hampered the viability, metastasis, radioresistance and promoted the apoptosis through suppressing cell glycolysis. MiR-501-3p was a direct target of circ-ZNF609, and si-circ-ZNF609-induced influence in PCa cells was partly alleviated by the addition of anti-miR-501-3p. MiR-501-3p functioned through directly interacting with and down-regulating HK2. HK2 was modulated by circ-ZNF609/miR-501-3p axis in PCa cells. Circ-ZNF609 silencing enhanced the radiosensitivity of PCa cells in vivo. Conclusion: Circ-ZNF609 promoted the progression and radioresistance of PCa cells through accelerating the glycolysis via miR-501-3p/HK2 axis, providing promising targets for improving the prognosis of PCa patients.

Identification of circRNA–miRNA–mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer

“…Following sanger sequencing, RNase R treatment and RT-qPCR analysis, the six DECs were validated and their decreased expression in GC tissues was confirmed. Previous studies have revealed that hsa_circ_0000615 acts as miRNA sponge to exert different roles in different solid tumors [ 37 – 40 ]; for example, hsa_circ_0000615 upregulates Sp1 expression by adsorbing miR-150-5p, and thereby promoting the proliferation and metastasis of nasopharyngeal cancer cells [ 38 ]. However, until now studies about the effect of hsa_circ_0000615 and the other five DECs on GC have been rarely reported.…”

Comprehensive Analysis of the Relationship Between Metabolic Reprogramming and Immune Function in Prostate Cancer

“… 33 For example, in prostate cancer, circular RNA could promote tumor progression and radioresistance by upregulating glycolysis. 34 Therefore, it will be a promising treatment to reverse the metabolic state of tumor with drugs. Studies have shown that sulforaphane can prevent the occurrence of prostate cancer by inhibiting glycolysis and fatty acid metabolism.…”

Circ_0067835 Knockdown Enhances the Radiosensitivity of Colorectal Cancer by miR-296-5p/IGF1R Axis

“… 10 , 11 Recently, some circRNAs have been shown to be transferred by exosomes and thus involve in human carcinogenesis and radioresistance development. 12 , 13 A previous report uncovered that circ_0067835 could inhibit cell proliferation and metastasis in endometrial carcinoma. 14 Importantly, circ_0067835 contributed to CRC development by regulating miR-1236-3p/homeobox B7 (HOXB7) axis.…”