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基于FOXO3a-ACSL4通路探讨circRNA CRIM1对非小细胞肺癌细胞生物学行为的影响

Exploring the effect of circRNA CRIM1 on the biological behavior of non-small cell lung cancer cells based on the FOXO3a-ASCL4 pathway

投稿时间：2024-12-27 修订日期：2025-04-17

DOI：

中文关键词: circRNA CRIM1 FOXO3a-ACSL4通路非小细胞肺癌 MMP-2 cleaved caspase-3 PCNA

英文关键词:circRNA CRIM1 FOXO3a-ASCL4 pathway non-small cell lung cancer MMP-2 cleaved caspase-3 PCNA

基金项目:河北省科学技术成果(20233509)

作者	单位	邮编
王小梅	张家口市第一医院	075000
郝建东^*	张家口市第一医院	075000
梁菲菲	张家口市第一医院

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中文摘要:

目的探讨circRNA CRIM1是否可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（Real-time polymerase chain reaction，RT-PCR）检测细胞正常肺上皮细胞BEAS-2B和NSCLC细胞circRNA CRIM1、FOXO3a和ACSL4 mRNA表达水平；将HCC827细胞分为对照（Control）组、si-NC组、si-circRNA CRIM1组、si-circRNA CRIM1+pc-NC组、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 mRNA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。两组间单独比较用t检验，单因素方差分析多组间差异，SNK-q检验组内两两差异。结果 NSCLC组织和细胞中circRNA CRIM1、FOXO3a和ACSL4 mRNA表达水平升高（P<0.05）；与Control组和si-NC组比较，si-circRNA CRIM1组HCC827细胞OD490（24h、48h）值和细胞增殖率、细胞划痕愈合率[（37.42±3.28）% vs （83.56±5.41）%，（82.79±5.63）%]和侵袭细胞数量[（69.78±8.46） vs （174.56±21.37），（168.31±19.84）]、circRNA CRIM1、FOXO3a mRNA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[（37.48±4.16）% vs （5.16±0.67）%，（5.31±0.72）%]、E-cadherin和cleaved caspase-3蛋白表达水平升高（P<0.05）；过表达FOXO3a可减弱沉默circRNA CRIM1表达对HCC827细胞生物学行为的抑制作用（P<0.05）。结论沉默circRNA CRIM1表达可抑制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:

Objective To investigate whether circRNA CRIM1 can affect the biological behavior of non-small cell lung cancer (NSCLC) cells by regulating the Forkhead Box O3a (FOXO3a)-Acyl-CoA Synthetase Long-Chain Family Member 4 pathway (ACSL4) pathway. Methods Detect the expression level of circRNA CRIM1, FOXO3a, ACSL4 mRNA in normal lung epithelial cells BEAS-2B and NSCLC cells by Real-time polymerase chain reaction (RT-PCR). HCC827 cells were assigned into Control group, si-NC group, si-circRNA CRIM1 group, si-circRNA CRIM1+pc-NC group, and si-circRNA CRIM1+pc-FOXO3a group. Cell proliferation, apoptosis, cell migration, invasion, circRNA CRIM1, FOXO3a mRNA and ACSL4 mRNA expression levels, FOXO3a and Epithelial cadherin (Epithelial cadherin, FOXO3a) were detected. E-cadherin), ACSL4, Neural cadherin (N-cadherin), Cysteine proteinase-3, and E-cadherin. cleaved caspase-3), Vimentin Intermediate Filament Protein (Vimentin Intermediate Filament Protein, vimentin), Proliferating Cell Nuclear Antigen (PCNA) and matrix metallopeptidase 2 (MMP-2) protein expression levels. The t test was used to compare the two groups separately, the difference between the groups was analyzed by one-way ANOVA, and the pairwise difference was tested by SNK-q. Results The mRNA expression levels of circRNA CRIM1, FOXO3a and ACSL4 in NSCLC tissues and cells were increased. (P<0.05). Compared with the Control group and the si-NC group, the OD490 (24h, 48h) value, cell proliferation rate, scratch healing rate[(37.42±3.28)% vs (83.56±5.41)%, (82.79±5.63)%], number of invasive cells[(69.78±8.46) vs (174.56±21.37), (168.31±19.84)], circRNA CRIM1, FOXO3a mRNA 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 [(37.48±4.16)% vs (5.16±0.67)%，(5.31±0.72)%], E-cadherin, and cleaved caspase-3 protein expression levels were higher (P<0.05). Overexpression of FOXO3a could weaken the inhibitory effect of silencing circRNA CRIM1 expression on the biological behavior of HCC827 cells (P<0.05). Conclusion Silencing circRNA CRIM1 expression can inhibit the malignant biological behavior of HCC827 cells, which may be related to the inhibition of the FOXO3a-ASCL4 pathway.

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