Circ_0000463 contributes to the progression and glutamine metabolism of non‐small‐cell lung cancer by targeting miR‐924/SLC1A5 signaling

Liu, Yunzhong; Wang, Shujun; Pan, Songli; Yan, Qingfeng; Liu, Yueping; Zhao, Ying

doi:10.1002/jcla.24116

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…Previous studies have shown that circSFMBT2 drove aggressive esophageal carcinoma phenotypes through the miR-107 dependence modulation for SLC1A5 [45]. Moreover, circ_0000463 is dedicated to the development and glutamine metabolism of NSCLC by targeting miR-924/SLC1A5 signaling [46], which is consistent with our work. SLC1A5 was considerably elevated and controlled by miR-330-3p negatively.…”

Section: Discussionsupporting

confidence: 92%

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5

Shi

Sui

et al. 2022

Journal of Immunology Research

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Background/Aim. Non-small-cell lung cancer (NSCLC) is the principal agent of cancer deaths globally. The goal of this study was to determine how circular RNA_0000518 (circ_0000518) regulates tumor progression. Materials/Methods. circ_0000518 was selected as a study target involved in NSCLC from GEO (Gene Expression Omnibus) database. circ_0000518 level was gauged by qRT-PCR. It was confirmed as circRNA by actinomycin D inhibition and RNase R assay. Subcellular localization of circ_0000518 was identified by FISH. Cell function was determined by CCK-8, Transwell, and western blot. Glutamine metabolic factors were detected by ELISA. The target regulation relationship between genes was clarified by dual-luciferase reporter assay. In vivo models were established to evaluate the impact of circ_0000518 on tumor growth. Immunohistochemical staining for Ki67, vimentin, and E-cadherin was used to detect cell proliferation and metastasis, respectively. Results. circ_0000518 expression was enhanced in NSCLC. si-circ_0000518 inhibited cell proliferation, invasion, and glutamine metabolism. circ_0000518 functioned as a molecular sponge for miR-330-3p, and inhibition of miR-330-3p in cells markedly reversed circ_0000518 interference-mediated antitumor effects. miR-330-3p interacted with 3 ′ -UTR of SLC1A5. miR-330-3p inhibitor-mediated protumor effect was remarkably reversed in cells after the knockdown of SLC1A5. circ_0000518 knockdown reduced glutamine, glutamate, and α-KG by targeting miR-330-3p. Intertumoral injection of circ_0000518 shRNA adeno-associated virus effectively halted xenograft tumor growth. Conclusion. The current study revealed that circ_0000518 may have a prooncogenic function in the formation and progression of NSCLC, which might be achieved through moderating the miR-330-3p/SLC1A5 axis.

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Section: Discussionsupporting

confidence: 92%

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5

Shi

Sui

et al. 2022

Journal of Immunology Research

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“…Increasing evidence has shown that circRNA expression was highly associated to clinical patient identities, while abnormal expression usually resulted in malignant behaviors like metastasis and proliferation 6 . Circ_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR‐924/SLC1A5 axis 21 . CircWHSC1 is an independent indicator of poor prognosis in NSCLC patients and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis 22 .…”

Section: Discussionmentioning

confidence: 99%

“… 6 Circ_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR‐924/SLC1A5 axis. 21 CircWHSC1 is an independent indicator of poor prognosis in NSCLC patients and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis. 22 Based on these results, it is essential to provide possible correlations between tumor progressions and the levels of circRNAs.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0041268 promotes NSCLC progress by sponging miR‐214‐5p/ROCK1

Yang¹,

Jin

2022

Clinical Laboratory Analysis

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Circular RNAs hold significant regulatory functions during various tumors. However, the exact hsa_circ_0041268 roles in non‐small cell lung cancer (NSCLC) along with regulatory mechanism are unknown. In this study, RT‐qPCR was used to perceive hsa_circ_0041268 expressions in NSCLC cell lines. Our team constructed small interfering RNA for hsa_circ_0041268. NSCLC cell proliferation, migration, and tumorigenesis in nude mice were assayed to confirm hsa_circ_0041268 activities in NSCLC cells. We then used bioinformatics and luciferase reporter analyses to characterize the hsa_circ_0041268 downstream targets. The result shows that the expressions of hsa_circ_0041268 incremented in NSCLC cell lines and hsa_circ_0041268 downregulation decreased cell proliferation and migration. ROCK1 and miR‐214‐5p were hsa_circ_0041268 downstream targets. miR‐214‐5p downregulation or ROCK1 overexpression restored migration and proliferation abilities after hsa_circ_0041268 silencing. ROCK1 overexpression renovated migration and proliferation abilities after miR‐214‐5p overexpression. In vivo investigations confirmed that hsa_circ_0041268 downregulation inhibited tumor formation and metastasis in nude mice xenografts. Together, results demonstrated that hsa_circ_0041268 acted as tumor promoter through novel hsa_circ_0041268/miR‐214‐5p/ROCK1 axis, which highlighted its potential as NSCLC therapeutic agent.

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“…The protein signals were visualized by BeyoECL Plus kit (Beyotime), and relative protein expression was analyzed via Image Lab software. Primary antibodies include anti-ki67 (1:1000, Abcam) [ 18 ], anti-Bax (1:1000, Abcam) [ 18 ], anti-E-cadherin (1:100, Abcam) [ 19 ], anti-SLC1A5 (1:1000, Abcam) [ 20 ], and anti-β-actin (1:2000, Abcam) [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Circ_0000808 promotes the development of non-small cell lung cancer by regulating glutamine metabolism via the miR-1827/SLC1A5 axis

2022

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Background Circular RNA (circRNA) has been proved to be an important molecular target for cancer treatment. However, the function and molecular mechanism of circ_0000808 in non-small cell lung cancer (NSCLC) are still unclear. Methods Quantitative real-time PCR was used to detect the expression of circ_0000808, miR-1827, and solute carrier family 1 member 5 (SLC1A5). Cell proliferation, apoptosis, migration, and invasion were measured by cell counting kit 8 assay, colony formation assay, EdU staining, flow cytometry, wound healing assay, and transwell assay. The protein expression was measured by Western blot analysis. Dual-luciferase reporter assay and RIP assay were used to investigate the interactions between miR-1827 and circ_0000808 or SLC1A5. Cell glutamine metabolism was assessed by determining glutamine uptake, glutamate production, and α-ketoglutarate production. Xenograft mouse model was used to assess the in vivo effects of circ_0000808. Results Circ_0000808 expression was upregulated in NSCLC tissues and cancer cells, and its silencing inhibited NSCLC cell proliferation, migration, and invasion and led to apoptosis. Further results confirmed that circ_0000808 interacted with miR-1827 to positively regulate SLC1A5. The rescue experiments showed that miR-1827 inhibitor reversed the suppressive effect of circ_0000808 knockdown on the malignant behaviors of NSCLC cells. Also, SLC1A5 overexpression abolished the inhibition effect of miR-1827 on NSCLC cell progression. In addition, circ_0000808/miR-1827/SLC1A5 axis positively regulated the glutamine metabolism process in NSCLC cells. Moreover, circ_0000808 knockdown reduced the NSCLC tumor growth in vivo. Conclusion In summary, our data showed that circ_0000808 enhanced the progression of NSCLC by promoting glutamine metabolism through the miR-1827/SLC1A5 axis.

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Circ_0000463 contributes to the progression and glutamine metabolism of non‐small‐cell lung cancer by targeting miR‐924/SLC1A5 signaling

Cited by 11 publications

References 29 publications

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5

Hsa_circ_0041268 promotes NSCLC progress by sponging miR‐214‐5p/ROCK1

Circ_0000808 promotes the development of non-small cell lung cancer by regulating glutamine metabolism via the miR-1827/SLC1A5 axis

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