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Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis.

Eur Rev Med Pharmacol Sci. 2020 Apr;24(7):3761-3774. doi:10.26355/eurrev_202004_20841
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摘要


OBJECTIVE:The present studies indicate that circRNAs play pivotal roles in human cancers. Lung adenocarcinoma (LUAC), one of lung cancer types, has high metastasis rate. Herein, we focused our study on the function and mechanism of circular RNA circCRIM1 in LUAC development. PATIENTS AND METHODS:Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circCRIM1, miR-125b-5p, and BTG anti-proliferation factor 2 (BTG2). Transwell assay was carried out to assess cell migration and invasion. The protein levels of BTG2, EMT markers, and HK2 were measured by Western blot. Glycolysis was analyzed through determining glucose consumption and lactate production. Furthermore, the targets of circCRIM1 and miR-125b-5p were predicted and verified by starBase and the dual-luciferase reporter assay, respectively. Also, whether circCRIM1 affecting tumor growth in vivo was explored using mouse xenograft assay. RESULTS:CircCRIM1 and BTG2 were downregulated, and miR-125b-5p was upregulated in LUAC tissues/cells. CircCRIM1 upregulation inhibited LUAC cell migration, invasion, epithelial-mesenchymal transition (EMT), glycolysis, and tumor growth. Moreover, circCRIM1 regulated LUAC cell development through targeting miR-125b-5p. MiR-125b-5p affected LUAC cell growth via binding to BTG2. Also, circCRIM1 promoted BTG2 expression by inhibiting miR-125b-5p expression in LUAC cells. CONCLUSIONS:CircCRIM1 was lowly expressed in LUAC. Moreover, circCRIM1 functioned as a sponge of miR-125b-5p to improve BTG2 expression, thereby suppressing LUAC development. Our finding indicated that circCRIM1 could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients.

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