Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

Cao, Lili; Wang, Min; Dong, Yaping; Xu, Bo; Chen, Ju; Ding, Yu; Qiu, Shusheng; Li, Liang; Zaharieva, Elena Karamfilova; Zhou, Xin‐Wen; Xu, Yujia

doi:10.1038/s41419-020-2336-0

Cited by 210 publications

(163 citation statements)

References 28 publications

(28 reference statements)

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“…In recent years, a wide variety of medical therapies have been proposed for Osteosarcoma, including surgery, chemotherapy, radiotherapy, hormonotherapy, and small molecular targeting treatments. Indeed, we have obtained promising results, as previously reported, the prognosis of OS patients without metastasis is generally excellent, and the five-year survival is greater than 60% [3]. Nevertheless, the prognosis of patients with advanced disease is very poor because of the recurrence and distant metastasis [4].…”

Section: Introductionsupporting

confidence: 61%

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

Pan

Zhang²,

Tang³

et al. 2020

Cancer Cell Int

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Background Recently, it has been demonstrated that circular RNA (circRNA) contributes to the production and progression in human cancer. However, the specific function and underlying mechanism of circ_0028171 in osteosarcoma (OS) still remain largely unclear and require to be investigated. Methods In our study, we confirmed differentially expressed circRNAs by microarray analysis in normal bone cells vs. OS cell lines. The expression of circ-0028171 in OS was measured by qRT-PCR. Nuclear-cytoplasmic fractionation was employed to identify the localization of circ-0028171, and RNase R and actinomycin D treatment were used to prove its circular characteristic. In vitro experiments, such as CCK-8 method, cell count, cell colony formation, transwell migration and invasion assays, and in vivo tumor models were adopted to evaluate the effect of circ_0028171. Further, luciferase reporter, RIP and RNA pull-down assays were conducted to confirm the binding sites of circ_0028171 with miR-218-5p. Results We found that circ_0028171 displayed a remarkably higher expression in both OS tissues and cell lines. Circ_0028171 mainly located in the cytoplasm as a stable cyclic transcript. Knockdown of circ_0028171 suppressed OS tumor growth in vitro and in vivo, while up-regulated circ_0028171 remarkably enhanced cell proliferation, migration and invasion abilities in OS. Several mechanistic experiments revealed that circ_0028171 served as a sponge of miR-218-5p to increase IKBKB expression. Conclusions our research reveals that circ_0028171 might promote the malignant behavior of OS tissues through miR-218-5p/IKBKB axis, which could be a potential novel marker for early diagnosis of OS.

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Section: Introductionsupporting

confidence: 61%

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

Pan

Zhang²,

Tang³

et al. 2020

Cancer Cell Int

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“…18 Cao et al claimed that circ-RNF20 accelerated the progression and glycolysis of breast cancer cells through regulating miR-487a/ HIF-1α/HK2 axis. 19 The expression pattern and working mechanism of HK2 in PCa were investigated in this study.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang²,

Ren

et al. 2020

CMAR

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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.

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“…36 It is characterized by high glucose uptake, active glycolysis and high lactate production in metabolites. 37 Reprogramming of energy metabolism consequently results in high accumulation of lactate in the tumour microenvironment. 38 Recent findings shown that lactate was positively correlated with higher incidence of metastases, tumour progression and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Lactate induced up‐regulation of KLHDC8A (Kelch domain‐containing 8A) contributes to the proliferation, migration and apoptosis of human glioma cells

Zhu

Chen

Yang

et al. 2020

J Cellular Molecular Medi

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Glioma is the most common tumour with the highest mortality rate in the central nervous system. 1 Glioma can be classified into three grades (II, III and IV) according to the 2016 World Health Organization (WHO) classification. 2 Among the three grades, grade II were subdivided as low-grade gliomas and grade III and IV were subdivided as high-grade gliomas. The 2015 annual report of the National Central Cancer Registry of China (NCCR) shows that the morbidity and mortality of glioma patients are increasing year by year. 3 Glioma possesses many characteristics, including highly invasive, rich blood vessels and high recurrence rate. 4 The traditional multi-modal therapy

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Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

Cited by 210 publications

References 28 publications

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

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

Lactate induced up‐regulation of KLHDC8A (Kelch domain‐containing 8A) contributes to the proliferation, migration and apoptosis of human glioma cells

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