Knockdown of circRNA circ_0087378 Represses the Tumorigenesis and Progression of Esophageal Squamous Cell Carcinoma Through Modulating the miR-140-3p/E2F3 Axis

Wang, Jing; Wang, Qiushuang; Gong, Yi; Qiu, Hu; Zhang, Haoliang; Shi, Ke; Chen, Yongshun

doi:10.3389/fonc.2020.607231

Cited by 21 publications

(19 citation statements)

References 35 publications

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“…29 Likewise, E2F3 had elevated levels in esophageal squamous cell carcinoma (ESCC), and circ_0087378 deficiency blocked ESCC cell progression by enhancing E2F3 expression. 30 Here, we discovered that the abundance of E2F3 was raised in EC tissues and cells. Moreover, E2F3 introduction relieved the suppressive influences of miR-493-5p overexpression on EC cell development.…”

Section: Discussionmentioning

confidence: 92%

circFIG 4 drives the carcinogenesis and metastasis of esophagus cancer via the miR‐493‐5p/E2F3 axis

2022

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Background: Esophageal cancer (EC) is a highly malignant tumor of the digestive tract. Circular RNAs (circRNAs) have been verified to play a regulatory role in the occurrence and progression of different cancers, including EC. This research aimed to investigate the role and molecular mechanism of circFIG 4 in EC progression. Methods: The analyses of circFIG 4, miR-493-5p, and neuro-oncological ventral antigen 2 levels were administrated by quantitative real-time polymerase chain reaction. The characteristics of circFIG 4 were determined by Ribonuclease R assay and Actinomycin D assay. Cell proliferation was assessed via colony formation assay and 5-ethynyl-2 0deoxyuridine incorporation assay. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Western blot was performed to assess protein expression. The targeted interaction among circFIG 4, miR-493-5p, and E2F transcription factor 3 (E2F3) were validated using dual-luciferase reporter or RNA immunoprecipitation assays. Results: circFIG 4 was overtly upregulated in EC and was relatively stable in EC cells. circFIG 4 knockdown impeded proliferation, migration, and invasion and expedited apoptosis in EC cells. circFIG 4 served as a miR-493-5p sponge to act in the development of EC. Furthermore, circFIG 4 modulated EC progression via targeting miR-493-5p and miR-493-5p suppressed EC progression via targeting E2F3. circFIG 4 modulated E2F3 expression through acting as a sponge of miR-493-5p. Moreover, circFIG 4 knockdown inhibited EC tumorigenesis by targeting miR-493-5p/E2F3 axis tumor growth in vivo. Conclusion: circFIG 4 silence mitigated EC malignant progression at least partly by mediating the miR-493-5p/E2F3 pathway, highlighting new biomarkers and therapeutic targets for EC treatment.

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Section: Discussionmentioning

confidence: 92%

circFIG 4 drives the carcinogenesis and metastasis of esophagus cancer via the miR‐493‐5p/E2F3 axis

2022

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“…CircNTRK2 was increased in ESCC tissue and involved in cell metastasis. This effect of circNTRK2 may be related to its interaction with miR-140-3p to weaken its suppression on E2F3 [ 63 ]. Another report revealed that circNTRK2 also sponge miR-140-3p to regulate the expression of NRIP1, bringing about the malignant cell behaviors of ESCC, including cell migration and invasion [ 64 ].…”

Section: Introductionmentioning

confidence: 99%

Current advances and future perspectives on the functional roles and clinical implications of circular RNAs in esophageal squamous cell carcinoma: more influential than expected

Wang

et al. 2022

Biomark Res

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Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive gastrointestinal cancers with high incidence and mortality. Therefore, it is necessary to identify novel sensitive and specific biomarkers for ESCC detection and treatment. Circular RNAs (circRNAs) are a type of noncoding RNAs featured by their covalently closed circular structure. This special structure makes circRNAs more stable in mammalian cells, coupled with their great abundance and tissue specificity, suggesting circRNAs may present enormous potential to be explored as valuable prognostic and diagnostic biomarkers for tumor. Mounting studies verified the critical roles of circRNAs in regulating ESCC cells malignant behaviors. Here, we summarized the current progresses in a handful of aberrantly expressed circRNAs, and elucidated their biological function and clinical significance in ESCC, and introduced a series of databases for circRNA research. With the improved advancement in high-throughput sequencing and bioinformatics technique, new frontiers of circRNAs will pave the path for the development of precision treatment in ESCC.

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“…E2F transcription factor 3 (E2F3), a member of E2F transcription factor family that controls DNA synthesis, cell cycle, and cell death, has been underscored as a strong oncogene in numerous tumors 16–19 . Moreover, E2F3 is involved in the carcinogenic mechanism of ESCC 20–22 . Furthermore, it is still undefined whether E2F3 can work as a downstream effector of circ_0000654 in regulating ESCC development.…”

Section: Introductionmentioning

confidence: 99%

A novel circ_0000654/miR‐375/E2F3 ceRNA network in esophageal squamous cell carcinoma

et al. 2022

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Background The competing endogenous RNA (ceRNA) activity of circular RNAs (circRNAs) has been implicated in the pathogenesis of cancers, including esophageal squamous cell carcinoma (ESCC). Here, we identified the ceRNA mechanism of circ_0000654 regulation in ESCC. Methods The levels of circ_0000654, E2F transcription factor 3 (E2F3), and microRNA (miR)‐375 were gauged by quantitative real‐time PCR (qRT‐PCR) and western blot. Cell proliferation was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays. Cell apoptosis was detected by flow cytometry. Cell colony formation was tested by colony formation assay. Dual‐luciferase reporter, RNA pull‐down and RNA immunoprecipitation (RIP) assays were performed to confirm the direct relationship between miR‐375 and circ_0000654 or E2F3. Xenograft model assays were used to evaluate the effect of circ_0000654 in vivo. Results Circ_0000654 and E2F3 were upregulated in ESCC. Circ_0000654 depletion enhanced cell apoptosis and hindered cell proliferation and glycolysis in vitro, as well as weakened tumor growth in vivo. Increased expression of E2F3 counteracted the effects of circ_0000654 depletion. Mechanistically, E2F3 was a target of miR‐375, and circ_0000654 modulated E2F3 expression through sequestering miR‐375. Furthermore, miR‐375 upregulation phenocopied circ_0000654 knockdown in inhibiting ESCC progression. Conclusion Our findings identify a new circ_0000654/miR‐375/E2F3 ceRNA crosstalk for the oncogenic role of circ_0000654 in ESCC and establish a notion that targeting circ_0000654 and its pathways may have the potential to improve ESCC outcome.

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Knockdown of circRNA circ_0087378 Represses the Tumorigenesis and Progression of Esophageal Squamous Cell Carcinoma Through Modulating the miR-140-3p/E2F3 Axis

Cited by 21 publications

References 35 publications

circFIG 4 drives the carcinogenesis and metastasis of esophagus cancer via the miR‐493‐5p/E2F3 axis

circFIG 4 drives the carcinogenesis and metastasis of esophagus cancer via the miR‐493‐5p/E2F3 axis

Current advances and future perspectives on the functional roles and clinical implications of circular RNAs in esophageal squamous cell carcinoma: more influential than expected

A novel circ_0000654/miR‐375/E2F3 ceRNA network in esophageal squamous cell carcinoma

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