| 王小梅,郝建东,梁菲菲.基于FOXO3a-ACSL4通路探讨环状RNA CRIM1对非小细胞肺癌细胞生物学行为的影响[J].肿瘤学杂志,2025,31(7):613-620. |
| 基于FOXO3a-ACSL4通路探讨环状RNA CRIM1对非小细胞肺癌细胞生物学行为的影响 |
| Effect of CircularRNA CRIM1 on Biological Behavior of Non-Small Cell Lung Cancer Cell and Its Relation with FOXO3a-ASCL4 Pathway |
| 投稿时间:2024-12-27 |
| DOI:10.11735/j.issn.1671-170X.2025.07.B007 |
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| 中文关键词: 非小细胞肺癌 环状RNA CRIM1 FOXO3a-ACSL4通路 基质金属肽酶2 增殖细胞核抗原 |
| 英文关键词:non-small cell lung cancer circularRNA CRIM1 FOXO3a-ASCL4 pathway matrix metallopeptidase 2 proliferating cell nuclear antigen |
| 基金项目:河北省科学技术成果(20233509) |
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| 中文摘要: |
| 摘 要:[目的] 探讨环状RNA(circular RNA,circRNA) CRIM1通过调控叉头盒蛋白O3a(forkhead box O3a,FOXO3a)长链脂酰辅酶A合成酶4(Acyl-CoA synthetase long-chain family member 4 pathway,ACSL4)通路影响非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞生物学行为。[方法] 实时荧光定量聚合酶链反应检测正常肺上皮细胞BEAS-2B和NSCLC细胞(16HBE、H460、HCC827、A549)circRNA CRIM1、FOXO3a和ACSL4 mRNA表达水平;并选取cirRNA CRIMI表达变化最明显的HCC827细胞用于后续研究。实验分为Control组、 si-NC组、si-circRNA CRIM1组、si-circRNA CRIM1+pc-NC组和si-circRNA CRIM1+pc-FOXO3a组。检测细胞增殖、细胞凋亡、细胞迁移、侵袭、circRNA CRIM1、FOXO3a和ACSL4 mRNA表达水平、FOXO3a、上皮钙黏蛋白(epithelial cadherin,E-cadherin)、ACSL4、神经钙黏蛋白(neural cadherin,N-cadherin)、半胱氨酸蛋白酶3(cysteine proteinase 3,Cleaved caspase-3)、波形蛋白中间丝蛋白(vimentin intermediate filament protein,Vimentin)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和基质金属肽酶2(matrix metallopeptidase 2,MMP-2)蛋白表达水平。[结果] NSCLC组织和细胞中circRNA CRIM1、FOXO3a和ACSL4 mRNA表达水平升高(P均<0.05)。与Control和si-NC组比较,si-circRNA CRIM1组HCC827细胞OD490(24 h、48 h)和细胞增殖率、细胞划痕愈合率和侵袭细胞数量、circRNA CRIM1、FOXO3a和ACSL4 mRNA表达水平、N-cadherin、Vimentin、MMP-2、PCNA、FOXO3a和ACSL4蛋白表达水平降低,细胞凋亡率、E-cadherin和Cleaved caspase-3蛋白表达水平升高(P均<0.05)。过表达FOXO3a可减弱低表达circRNA CRIM1对HCC827细胞生物学行为的抑制作用(P<0.05)。[结论] 低表达circRNA CRIM1可抑制HCC827细胞恶性生物学行为,可能与抑制FOXO3a-ACSL4通路有关。 |
| 英文摘要: |
| Abstract:[Objective] To investigate the effect of circular RNA(circRNA) CRIM1 biological behaviors of non-small cell lung cancer(NSCLC) cells and its relation with the forkhead box O3a-acyl-CoA synthetase long-chain family member 4(FOXO3a-ACSL4) signaling pathway. [Methods] The expression levels of circRNA CRIM1, FOXO3a, ACSL4 mRNA in normal lung epithelial BEAS-2B cells and NSCLC(16HBE, H460, HCC827, A549) cells were detected by real-time polymerase chain reaction, HCC827 cells were selected for the subsequent research based with the most significant change in cirRNA CRIMI etpression. The experiment were assigned into control, si-NC, si-circRNA CRIM1, si-circRNA CRIM1+pc-NC, and si-circRNA CRIM1+pc-FOXO3a groups. Cell proliferation, cell apoptosis, cell migration and invasion abilities were determined. The mRNA expression levels of circRNA CRIM1 ,FOXO3a and ACSL4. The protein expresson levels of FOXO3a, epithelial cadherinl(E-cadherin), ACSL4, neural cadherin (N-cadherin), cysteine proteinase 3, vimentin intermediate filament protein(Vimentin), proliferating cell nuclear antigen(PCNA) and matrix metallopeptidase 2(MMP-2) were detected. [Results] The mRNA expression levels of circRNA CRIM1, FOXO3a and ACSL4 in NSCLC tissues and cells were increased (all P<0.05). Compared with the control group and the si-NC group, the OD490 (24 h, 48 h), cell proliferation rate, scratch healing rate, number of invasive cells, circRNA CRIM1, FOXO3a and ACSL4 mRNA expression levels, N-cadherin, Vimentin, MMP-2, PCNA, FOXO3a and ACSL4 protein expression levels of HCC827 cells in the si-circRNA CRIM1 group were lower, the apoptosis rate, E-cadherin, and Cleaved caspase-3 protein expression levels were higher (all P<0.05). Overexpression of FOXO3a attenuated the inhibitory effect of low expression CRIM1 on the biological behavior of HCC827 cells (P<0.05). [Conclusion] Low expression of circRNA CRIM1 can inhibit the malignant biological behavior of HCC827 cells, which may be related to the inhibition of the FOXO3a-ASCL4 signaling pathway. |
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