Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma

Zhong, Qian; Huang, Juncong; Wei, Jiawang; Wu, Renrui

doi:10.1186/s12935-019-0959-y

Cited by 81 publications

(67 citation statements)

References 35 publications

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“…Ke et al found that CircHIPK3 promoted NPC cell invasion and proliferation through targeting the miR-4288/ELF3 axis [16]. Zhong et al demonstrated that cRNA CDR1 promotes NPC cell invasion and proliferation by regulating the miR-7-5p/E2F3 axis [17]. However, the functions as well as underlying mechanisms of circRNAs in NPC development are still not well known.…”

Section: Discussionmentioning

confidence: 99%

Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis

Liu¹,

Zhou²,

Zhang³

et al. 2020

J. Cancer

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Growing evidence has demonstrated that in tumor progression, circular RNAs (circRNAs) play important roles. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) have not been fully elucidated. In this study, it was demonstrated that that hsa_circ_0033074 (circSERPINA3) expression was found to be significantly upregulated in NPC tissues and cell lines. CircSERPINA3 inhibition significantly attenuated the invasion and proliferation abilities of NPC cells. The mechanism by which circSERPINA3 interacted with miR-944 was identified and MDM2 was demonstrated to function as a target gene of miR-944. Rescue experiments showed that miR-944 inhibitors or MDM2 overexpression reserved the effects of circSERPINA3 knockdown on NPC progression. Therefore, our study uncovered the circSERPINA3/miR-944/MDM2 axis in NPC, which may be a potential NPC therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis

Liu¹,

Zhou²,

Zhang³

et al. 2020

J. Cancer

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“…We look forward to seeing in future studies whether the ndings of this paper apply to other tumors, such as ovarian cancer or even to other diseases. Previous reports revealed that a certain circRNA formed by cyclization of lncRNA may have different functions and mechanisms in different biological process, such as the CDR1as [21,48,49]. Thus, future iterations of comprehensive understanding of circCDKN2B-AS1 biogenesis, binding proteins/microRNAs, effects on aerobic glycolysis and tumorigenesis programs may in fact demonstrate even greater potency.…”

Section: Discussionmentioning

confidence: 99%

CircCDKN2B-AS1 Interacts with IMP3 to Stabilize Hexokinase 2 mRNA and Facilitate Cervical Squamous Cell Carcinoma Aerobic Glycolysis Progression

Zhang

Zhao

Yang

et al. 2020

Preprint

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Background: Circular RNAs(circRNAs) have been reported to play key roles in the development of various cancers. However, the biological function and clinical significance of most circRNAs are still elusive. The purpose of this study is to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development, and its potential value in clinic. Methods: The qRT-PCR array was conducted to verify the expression level of circCDKN2B-AS1. CCK8 assay, transwell assay, and FCM were undertaken to detect cellular proliferation, migration, and apoptosis, respectively. Seahorse XFe 96 analyzer was used to measure the glycolysis metabolism level. RNA pulldown, RIP, actinomycin-D adding assay and Western Blot were used to screen and elucidate the potential mechanisms. BALB/c nude mice and zebrafish embryo（AB,WT） were used as animal models to investigate tumorigenesis capability.18FDG-microPET/CT was used to detect the glucose metabolism level of subcutaneous tumor in nude mice. Results: CircCDKN2B-AS1, circular isoform of lncRNA CDKN2B-AS1, was upregulated in cervical cancer and precancer tissues. We found that circCDKN2B-AS1 associated with IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2(HK2) mRNA, the rate-limiting enzyme of aerobic glycolysis pathway. The expression level of circCDKN2B-AS1 fated the binding of IMP3 to 3’UTR of HK2 mRNA, consequently affects cell malignant phenotypes and aerobic glycolysis of cervical cancer in vitro and in vivo. Mutant circCDKN2B-AS1 lacking of the IMP3 binding site didn’t have such effects. Utilizing an inhibitory peptide to block the interaction between circCDKN2B-AS1 and IMP3 protein impeded the binding of IMP3 to 3’UTR of HK2 mRNA and suppressed aerobic glycolysis in cervical cancer cells.Conclusions: Our findings demonstrate that circCDKN2B-AS1 facilitates aerobic glycolysis by sponging IMP3 protein to stabilize HK2 mRNA, consequently promotes malignant phenotypes in cervical cancer, which may provide a potential approach for cervical cancer therapeutics.

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“…The E2F family of transcription factors regulates the cell cycle, proliferation and apoptosis (29,30). E2F3 has been reported to be involved in various types of human cancer, including nasopharyngeal carcinoma (31), hepatocellular carcinoma (32) and bladder cancer (33). It was demonstrated that E2F3 is upregulated in HCC compared with normal controls, and that overexpression of E2F3 could be associated with a poor prognosis in HCC (34).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D3 mediates miR‑15a‑5p inhibition of liver cancer cell proliferation via targeting E2F3

Lin

Chang

et al. 2020

Oncol Lett

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Vitamin D3 has been demonstrated to suppress the development and progression of liver cancer, but the mechanism is unclear. The effects of vitamin D3 and microRNA (miR)-15a-5p on liver cancer cells were investigated in the present study using MTT and colony formation assays, flow cytometry, western blotting and reverse transcription-quantitative PCR. A dual-luciferase reporter assay was performed to determine whether E2F transcription factor 3 (E2F3) was a target of miR-15a-5p. The effects of silencing the E2F3 gene expression in liver cancer cells were investigated using a small interfering RNA. Vitamin D3 suppressed liver cancer cell proliferation, induced apoptosis and increased miR-15a-5p expression. Treatment with the miR-15a-5p mimics significantly suppressed liver cancer cell proliferation compared with that of the controls. Bioinformatics analysis and a dual-luciferase reporter assay demonstrated that E2F3 was a target of miR-15a-5p and that silencing E2F3 inhibited liver cancer cell proliferation. Therefore, Vitamin D3 suppressed cell proliferation by miR-15a-5p-mediated silencing of E2F3 gene expression. These findings suggested a role for vitamin D3 and E2F3 targeting as potential novel liver cancer therapies.

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Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma

Cited by 81 publications

References 35 publications

Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis

Cell proliferation and invasion is promoted by circSERPINA3 in nasopharyngeal carcinoma by regulating miR-944/MDM2 axis

CircCDKN2B-AS1 Interacts with IMP3 to Stabilize Hexokinase 2 mRNA and Facilitate Cervical Squamous Cell Carcinoma Aerobic Glycolysis Progression

Vitamin D3 mediates miR‑15a‑5p inhibition of liver cancer cell proliferation via targeting E2F3

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