LncRNA FGD5-AS1通过miR-103a-3p/RNF38轴影响结肠癌细胞的恶性生物学行为

doi:10.3969/j.issn.1006-6233.2025.01.003

摘要
图/表
参考文献
相关文章 (0)

全文: PDF (1772 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要 目的: 探讨长链非编码RNA FGD5反义RNA1(LncRNA FGD5-AS1)靶向调控miR-103a-3p/环指蛋白38(RNF38)轴对结肠癌细胞恶性生物学行为的影响。方法: 使用荧光定量PCR检测LncRNA FGD5-AS1、miR-103a-3p在人结肠黏膜上皮细胞和人结肠癌细胞SW480中的表达水平;通过StarBase和TargetScan数据库分析LncRNA FGD5-AS1、miR-103a-3p、RNF38之间的结合位点,使用双荧光酶报告基因检测进一步验证;将SW480细胞随机分为对照(Control)组、pcDNA-NC组、pcDNA-FGD5-AS1组、si-NC组、si-FGD5-AS1组、si-FGD5-AS1＋inhibitor NC组、si-FGD5-AS1＋miR-103a-3p inhibitor组,通过CCK-8、流式细胞术、Transwell试验、荧光定量PCR及Western blot法检测细胞增殖、凋亡、侵袭、FGD5-AS1、miR-103a-3p水平及RNF3蛋白表达水平。结果: 与人结肠黏膜上皮细胞相比,SW480细胞中LncRNA FGD5-AS1表达水平显著降低(1.00±0.00比0.48±0.10,t=12.737,P<0.05),miR-103a-3p表达水平显著升高(1.00±0.00比1.61±0.18,t=8.301,P<0.05);LncRNA FGD5-AS1可靶向负调控miR-103a-3p表达(P<0.05);miR-103a-3p可靶向正调控RNF38表达(P<0.05);与pcDNA-NC组相比,pcDNA-FGD5-AS1组SW480细胞中FGD5-AS1水平升高(0.98±0.10比2.34±0.45,t=7.227,P<0.05),细胞凋亡率增加(8.64±1.32比16.21±2.75,t=6.079,P<0.05),而miR-103a-3p表达水平(1.01±0.12比0.42±0.07,t=10.403,P<0.05)、RNF38蛋白表达水平(0.59±0.09比0.32±0.17,t=3.438,P=0.006)、细胞增殖活性(0.63±0.09比0.34±0.06,t=6.567,P<0.05)、细胞侵袭能力(112.63±14.94比43.82±5.67,t=10.548,P<0.05)降低。si-FGD5-AS1组细胞变化趋势与pcDNA-FGD5-AS1组相反,且miR-103a-3p inhibitor可逆转si-FGD5-AS1组的变化(P<0.05)。结论: 干扰LncRNA FGD5-AS1可能通过靶向上调miR-103a-3p,促进RNF38蛋白表达,从而提高结肠癌细胞增殖和侵袭能力,降低结肠癌细胞凋亡率,而上调LncRNA FGD5-AS1可抑制结肠癌细胞的恶性生物学行为。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章

关键词 ：结肠癌细胞, 长链非编码RNAFGD5反义RNA1, 微小RNA-103a-3p, 环指蛋白38

Abstract：Objective: To investigate the effect of long-chain non coding RNA FGD5 antisense RNA1 (LncRNA FGD5-AS1) on the malignant biological behavior of colon cancer cells via targeting the miR-103a-3p/RNF38 axis. Methods: Fluorescence quantitative PCR was used to detect the expression of LncRNA FGD5-AS1 and miR-103a-3p in human colon epithelial cells and human colon cancer SW480. StarBase and Targeted Scan databases were applied to analyze the binding sites between LncRNA FGD5-AS1, miR-103a-3p, and RNF38, and further validation was used by dual luciferase reporter for gene detection. SW480 cells were randomly grouped into control group, pcDNA NC group, pcDNA-FGD5-AS1 group, si-NC group, si-FGD5-AS1 group, si-FGD5-AS1+inhibitor NC group, and si-FGD5-AS1+miR-103a-3p inhibitor group. The cell counting kit-8 (CCK-8) assay, flow cytometry, Transwell assay, fluorescence quantitative PCR, and Western blot were applied to detect cell proliferation, apoptosis, invasion, FGD5-AS1, miR-103a-3p levels, and RNF3 protein expression level. Results: Compared with human colonic epithelial cells, the expression level of LncRNA FGD5-AS1 in SW480 cells was significantly reduced (1.00±0.00 vs 0.48±0.10, t=12.737, P<0.05), while the expression level of miR-103a-3p was significantly increased (1.00±0.00 vs 1.61±0.18, t=8.301, P<0.05). LncRNA FGD5-AS1 could target and negatively regulate miR-103a-3p expression (P<0.05). MiR-103a-3p could target and positively regulate RNF38 expression (P<0.05). Compared with the pcDNA NC group, the level of FGD5-AS1 in SW480 cells of the pcDNA-FGD5-AS1 group significantly increased (0.98±0.10 vs 2.34±0.45, t=7.227, P<0.05), and the apoptosis rate significantly increased (8.64±1.32 vs 16.21±2.75, t=6.079, P<0.05), while the expression levels of miR-103a-3p (1.01±0.12 vs 0.42±0.07, t=10.403, P<0.05), RNF38 protein expression levels (0.59±0.09 vs 0.32±0.17, t=3.438, P=0.006), cell proliferation activity (0.63±0.09 vs 0.34±0.06, t=6.567, P<0.05), and cell invasion ability (112.63±14.94 vs 43.82±5.67, t=10.548, P<0.05) significantly decreased. The change trend of the si-FGD5-AS1 group was opposite to that of the pcDNA-FGD5-AS1 group, and miR-103a-3p inhibitor could reverse the changes of the si-FGD5-AS1 group (P<0.05). Conclusion: Interference with LncRNA FGD5-AS1 may promote RNF38 protein expression via targeting upregulate miR-103a-3p, thereby enhancing proliferation and invasion abilities of colon cancer cells, and reducing apoptosis rate. Upregulation of LncRNA FGD5-AS1 can inhibit the malignant biological behavior of colon cancer cells.

Key words： Colon cancer cells Long-chain non coding RNA FGD5 antisense RNA1 MicroRNA-103a-3p Ring finger protein 38

基金资助:黑龙江省中医药科研项目,(编号:ZHY2020-128)

通讯作者: 马静

引用本文:

石沛, 庞雪莹, 邓升华, 祝金华, 赵士梅, 马秀岩, 马静. LncRNA FGD5-AS1通过miR-103a-3p/RNF38轴影响结肠癌细胞的恶性生物学行为[J]. 河北医学, 2025, 31(1): 15-21.
SHI Pei, PANG Xueying, DENG Shenghua, et al. Effect of LncRNA FGD5-AS1 on Malignant Biological Behavior of Colon Cancer Cells via Targeting miR-103a-3p/RNF38 Axis. HeBei Med, 2025, 31(1): 15-21.

链接本文:

http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.01.003 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I1/15

[1] Wang Y,Yan Q,Fan C,et al.Overview and countermeasures of cancer burden in China[J].Sci China Life Sci,2023,66(11):2515-2526.
[2] Miller KD,Nogueira L,Devasia T,et al.Cancer treatment and survivorship statistics,2022[J].CA Cancer Clin,2022,72(5):409-436.
[3] Gong Y,Zhu W,Sun M,et al.Bioinformatics analysis of long non-coding RNA and related diseases:an overview[J].Front Genet,2021,8(12):813873.
[4] Chen S,Shen X.Long noncoding RNAs:functions and mechanisms in colon cancer[J].Mol Cancer,2020,19(1):167.
[5] 廖薇薇,傅祥炜,温必盛,等.lncRNA CASC11靶向调控miR-146a-3p对结肠癌细胞增殖、侵袭的影响[J].华中科技大学学报(医学版),2023,52(6):803-809.
[6] Fang K,Xu ZJ,Jiang SX,et al.LncRNA FGD5-AS1 promotes breast cancer progression by regulating the hsa-miR-195-5p/NUAK2 axis[J].Mol Med Rep,2021,23(6):460.
[7] Feng L,Zheng H,Zhang H,et al.LncRNA FGD5-AS1 drives the malignant development of gastric cancer by negatively interacting with FZD3[J].Pol Pathol,2022,73(1):72-79.
[8] Zhang ML,Sun WH,Wu HQ,et al.Knockdown of microRNA-103a-3p inhibits the malignancy of thyroid cancer cells through Hippo signaling pathway by upregulating LATS1[J].Neoplasma,2020,67(6):1266-1278.
[9] Madeo G,Bonetti G,Gadler M,et al.Omics sciences and precision medicine in colon cancer[J].Clin Ter,2023,174(Suppl 2):55-67.
[10] Luo Y,Chen JJ,Lv Q,et al.Long non-coding RNA NEAT1 promotes colorectal cancer progression by competitively binding miR-34a with SIRT1 and enhancing the Wnt/β-catenin signaling pathway[J].Cancer Lett,2019,440(441):11-22.
[11] Ge C,Dong J,Chu Y,et al.LncRNA FGD5-AS1 promotes tumor growth by regulating MCL1 via sponging miR-153-3p in oral cancer[J].Aging (Albany NY),2020,12(14):14355-14364.
[12] Wang H,Huang H,Wang L,et al.Cancer-associated fibroblasts secreted miR-103a-3p suppresses apoptosis and promotes cisplatin resistance in non-small cell lung cancer[J].Aging (Albany NY),2021,13(10):14456-14468.
[13] Zhou X,Jin J,Wang W,et al.Efficacy and adverse reactions of combination therapy of bevacizumab and 5-fluorouracil in patients with metastatic colon cancer[J].BUON,2019,24(2):494-500.
[14] Ji J,Jing A,Ding Y,et al.FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression[J].Cell Death Dis,2024,15(1):33.