首页|CircCCND1 调节 miR-340-5p/TGIF1 轴对H446肺癌细胞恶性生物学行为的影响

CircCCND1 调节 miR-340-5p/TGIF1 轴对H446肺癌细胞恶性生物学行为的影响

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背景与目的 肺癌是常见的肺部恶性肿瘤,探究肺癌发生发展的分子机制是当前研究的热点.环状RNA细胞周期蛋白D1(circular RNA Cyclin D1,CircCCND1)在肺癌中高表达,可能是治疗肺癌的潜在靶点.本研究旨在探讨CircCCND1调节miR-340-5p/转化生长因子β诱导因子同源框 1(transforming growth factor β-induced factor homeobox 1,TGIF1)轴对肺癌细胞恶性生物学行为的影响.方法 检测人正常肺上皮细胞BEAS-2B及人肺癌H446细胞中CircCCND1、miR-340-5p及TGIF1 mRNA表达.将体外培养的H446细胞分为对照组、CircCCND1 siRNA组、miR-340-5p mimics组、阴性对照组、CircCCND1 siRNA+miR-340-5p inhibitor组,检测细胞增殖、线粒体膜电位、凋亡、迁移和侵袭情况,以及各组细胞 CircCCND1、miR-340-5p、TGIF1 mRNA、BCL2 相关 X 蛋白(BCL2-associated X protein,Bax)、剪切的半胱天冬氨酸蛋白酶3(cleaved Caspase-3)、N-钙黏蛋白(N-cadherin)、E-钙黏蛋白(E-cadherin)、TGIF1蛋白表达,并验证miR-340-5p与CircCCND1、TGIF1的靶向关系.结果 与BEAS-2B细胞相比,H446细胞CircCCND1、TGIF1 mRNA升高,miR-340-5p表达降低(P<0.05).敲低CircCCND1或上调miR-340-5p表达可抑制H446细胞增殖、迁移、侵袭,降低TGIF1 mRNA和TGIF1蛋白表达,促进细胞凋亡;下调miR-340-5p可拮抗敲低CircCCND1对H446肺癌细胞恶性生物学行为的抑制作用.CircCCND1可能靶向下调miR-340-5p,miR-340-5p可能靶向下调TGIF1.结论 敲低CircCCND1可抑制肺癌H446细胞恶性行为,其作用可能是通过调控miR-340-5p/TGIF1轴实现的.
Effect of CircCCND1 on the Malignant Biological Behaviors of H446 Lung Cancer Cells by Regulating the MiR-340-5p/TGIF1 Axis
Background and objective Lung cancer is a common malignant tumor of the lung.To explore the molecular mechanism of the occurrence and development of lung cancer is a hot topic in current research.Cyclic RNA D1(CircCCND1)is highly expressed in lung cancer and may be a potential target for the treatment of lung cancer.The aim of this study was to investigate the effect of CircCCND1 on the malignant biological behaviors of lung cancer cells by regulat-ing the miR-340-5p/transforming growth factor β-induced factor homeobox 1(TGIF1)axis.Methods The expression of CircCCND1,miR-340-5p,and TGIF1 mRNA in human normal lung epithelial cells BEAS-2B and human lung cancer H446 cells were detected.H446 cells cultured in vitro were randomly divided into control group,CircCCND1 siRNA group,miR-340-5p mimics group,negative control group,and CircCCND1 siRNA+miR-340-5p inhibitor group.Cell proliferation,mito-chondrial membrane potential,apoptosis,migration,and invasion were detected,and the expressions of CircCCND1,miR-340-5p,TGIF1 mRNA,BCL2-associated X protein(Bax),cleaved Caspase-3,N-cadherin,E-cadherin,and TGIF1 proteins in each group were detected.The targeting relationship of miR-340-5p with CircCCND1 and TGIF1 was verified.Results Compared with BEAS-2B cells,CircCCND1 and TGIF1 mRNA were increased in H446 cells,and miR-340-5p expression was decreased(P<0.05).Knocking down CircCCND1 or up-regulating the expression of miR-340-5p inhibited the proliferation,migration and invasion of H446 cells,decreased the expression of TGIF1 mRNA and TGIF 1 protein,and promoted cell apop-tosis.Down-regulation of miR-340-5p could antagonize the inhibitory effect of CircCCND1 knockdown on the malignant bio-logical behavior of H446 lung cancer cells.CircCCND1 may target the down-regulation of miR-340-5p,and miR-340-5p may target the down-regulation of TGIF 1.Conclusion Knocking down CircCCND1 can inhibit the malignant behaviors of lung cancer H446 cells,which may be achieved through the regulation of miR-340-5p/TGIF1 axis.

CircCCND1miR-340-5p/TGIF1Lung neoplasmsMalignant biological behavior

董怡、朱翠敏、柳新、赵继伟、李青山

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067000 承德,承德医学院附属医院肿瘤科

CircCCND1 miR-340-5p/TGIF1 肺肿瘤 恶性生物学行为

河北省自然科学基金面上项目

H2020406050

2024

中国肺癌杂志
中国抗癌协会 中国防痨协会 天津医科大学总医院

中国肺癌杂志

CSTPCD北大核心
影响因子:1.397
ISSN:1009-3419
年,卷(期):2024.27(3)
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