Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer

Tan, Shuangyan; Sun, Dan; Pu, Wenchen; Gou, Qinglong; Guo, Chenglin; Gong, Youling; Li, Jiao; Wei, Yuquan; Liu, Lunxu; Zhao, Yun; Peng, Yong

doi:10.1186/s12943-018-0887-9

Cited by 119 publications

(93 citation statements)

References 10 publications

(10 reference statements)

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“…circPRKCI functioned as a sponge for both miR‐545 and miR‐589 and abrogated their suppression of the protumorigenic transcription factor E2F7 . Similarly, the echinoderm microtubule associated protein‐like 4—anaplastic lymphoma kinase (EML4‐ALK)‐v3b‐derived circRNA, F‐circEA‐2a, promotes cell migration and invasion, supporting the significant diagnostic value of EML4‐ALK‐positive non‐small‐cell lung cancer . These studies exemplify circRNAs as oncogenes contributing to LUAC progression.…”

Section: Discussionsupporting

confidence: 85%

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

et al. 2019

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In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin‐coupled microRNA capture were carried out to investigate the Ago2‐dependent interaction of circCRIM1 and microRNA (miR)‐93/miR‐182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well‐known tumor suppressor, by sponging miR‐93 and miR‐182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target.

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Section: Discussionsupporting

confidence: 85%

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

et al. 2019

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“…CircRNAs are dysregulated in many cancers, such as breast cancer, colorectal cancer, ovarian cancer, lung cancer, hepatocellular carcinoma, and basal cell carcinoma . However, to date, their roles in cancer glucose metabolism reprogramming have not been reported.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR‐338‐3p/PKM2 Axis Under Hypoxic Stress

et al. 2019

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Glucose metabolism reprogramming, which is a well‐established characteristic of multiple cancers, demands a higher rate of glycolysis to meet the increasing demands for macromolecular synthesis and to maintain rapid proliferation in a hypoxic environment. However, the mechanism underlying this switch remains to be elucidated. In this study, we investigated the function of circular RNA MAT2B (circMAT2B) in hepatocellular carcinoma (HCC) glucose metabolism reprogramming and malignancy. CircMAT2B was identified by bioinformatics analysis of Gene Expression Omnibus data sets. CircMAT2B expression was up‐regulated in HCC tissues and cell lines. HCC patients with high circMAT2B expression had shortened overall survival. We analyzed the positive correlation between glycolysis and circMAT2B expression in HCC using a maximum standardized uptake value determined by preoperative positron emission tomography/computed tomography scanning combined with high‐performance liquid chromatography assessment of the metabolites of glycolysis and the citric acid cycle. The effect of circMAT2B on glycolysis was validated in vitro and in vivo under hypoxic (1% O2) conditions. Functional assays were performed in HCC cells, HCC organoids, and nude mice to explore the tumor‐promoting roles of circMAT2B in HCC. Biotin‐coupled probe pull‐down assays, biotin‐coupled microRNA capture, luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation assays were performed to confirm the interaction among different RNAs. Mechanistically, we demonstrated that circMAT2B up‐regulated expression levels of the microRNA (miR)‐338‐3p target gene PKM2, which encodes a key enzyme in the process of glycolysis, through “sponging” miR‐338‐3p; thus, glycolysis and HCC progression are promoted through this mechanism. Conclusion: CircMAT2B promoted HCC progression by enhanced glycolysis by activating the circMAT2B/miR‐338‐3p/PKM2 axis under hypoxia, which may provide a therapeutic target for HCC.

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“…Wang et al, 2019). CircRNA F-circEA-2a contributed to cell migration and invasion but had little role in cell proliferation (Tan et al, 2018). A former study obtained dozens of circRNAs through the CircBase database and CSCD database for comparison between lung adenocarcinoma tissues and paired non-tumor tissues (Liu et al, 2019), and circ_0005962, back-spliced from tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), was one of the significantly upregulated circRNAs and had valuable prognostic significance.…”

Section: Introductionmentioning

confidence: 99%

Circ_0005962 functions as an oncogene to aggravate non-small cell lung cancer progression via circ_0005962/miR-382-5p/PDK4 regulatory network

Zhenxiu¹,

Chen²,

Peng³

et al. 2020

Preprint

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Non-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs (circRNAs) were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms. The expression of circ_0005962, miR-382-5p and pyruvate dehydrogenase kinase 4 (PDK4) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), PDK4, Cleaved Caspase 3 (C-caspase 3) and proliferating cell nuclear antigen (PCNA) were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. The interaction between miR-382-5p and circ_0005962 or PDK4 was predicted by the online tool CircInteractome or starbase and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft model was constructed to investigate the role of circ_0005962 in vivo. circ_0005962 expressed with a high level in NSCLC tissues and cells. Circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. MiR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. Circ_0005962 knockdown suppressed tumor growth in vivo. Circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.

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Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer

Cited by 119 publications

References 10 publications

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR‐338‐3p/PKM2 Axis Under Hypoxic Stress

Circ_0005962 functions as an oncogene to aggravate non-small cell lung cancer progression via circ_0005962/miR-382-5p/PDK4 regulatory network

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