
浏览全部资源
扫码关注微信
1.康复大学青岛中心医院,消化内科,山东青岛
2.康复大学青岛中心医院,内镜中心,山东青岛
郑英兰,E-mail:wtsgnc@163.com
收稿:2025-10-14,
修回:2025-11-28,
纸质出版:2025-12-30
移动端阅览
李娜,李浩,林坤,等.LncRNA FGD5-AS1通过调节miR-302b-3p/E2F1轴对胃癌细胞迁移及侵袭的影响[J].陆军军医大学学报,2025,47(24):3065-3076.DOI:10.16016/j.2097-0927.202510027.
LI N,LI H,LIN K,et al.Effects of LncRNA FGD5-AS1 on migration and invasion of gastric cancer cells by regulating miR-302b-3p/E2F1 axis[J].J Army Med Univ,2025,47(24):3065-3076.DOI:10.16016/j.2097-0927.202510027.
李娜,李浩,林坤,等.LncRNA FGD5-AS1通过调节miR-302b-3p/E2F1轴对胃癌细胞迁移及侵袭的影响[J].陆军军医大学学报,2025,47(24):3065-3076.DOI:10.16016/j.2097-0927.202510027. DOI:
LI N,LI H,LIN K,et al.Effects of LncRNA FGD5-AS1 on migration and invasion of gastric cancer cells by regulating miR-302b-3p/E2F1 axis[J].J Army Med Univ,2025,47(24):3065-3076.DOI:10.16016/j.2097-0927.202510027. DOI:
目的
2
探讨长链非编码RNA FGD5-AS1(LncRNA FGD5-AS1)调节微小RNA-302b-3p(miR-302b-3p)/E2F转录因子1(E2F1)轴对胃癌细胞迁移及侵袭的影响。
方法
2
实时荧光定量PCR反应(qRT-PCR)检测胃癌细胞系(SGC-7901、MKN-45、HGC-27、AGS、BGC-823)及人胃粘膜上皮细胞系GES-1中LncRNA FGD5-AS1、miR-302b-3p、E2F1 mRNA表达,筛选最佳干预细胞。将胃癌细胞分为对照组(NC组)、sh-NC组、sh-FGD5-AS1组、sh-FGD5-AS1+anti-miR-NC组、sh-FGD5-AS1+anti-miR-302b-3p组。qRT-PCR检测细胞中LncRNA FGD5-AS1、miR-302b-3p、E2F1 mRNA的表达水平;MTT法及流式细胞仪分别检测细胞增殖与凋亡;划痕实验及Transwell实验分别检测细胞迁移与侵袭;Western blot检测E2F1、Ki-67、Bax、Bcl-2蛋白表达;裸鼠移植瘤实验验证LncRNA FGD5-AS1对胃癌移植瘤生长的影响;双荧光素酶报告基因和RNA pull-down实验检测LncRNA FGD5-AS1、E2F1与miR-302b-3p的靶向关系。
结果
2
与GES-1相比,胃癌细胞系(SGC-7901、MKN-45、HGC-27、AGS、BGC-823)中LncRNA FGD5-AS1、E2F1 mRNA表达水平升高,miR-302b-3p表达水平降低(
P
<
0.05),选择AGS细胞进行实验;沉默LncRNA FGD5-AS1表达可显著上调miR-302b-3p表达,下调E2F1表达,抑制胃癌细胞增殖、迁移与侵袭,促进细胞凋亡(
P
<
0.05);抑制miR-
302b-3p表达可部分减弱沉默LncRNA FGD5-AS1对胃癌细胞增殖、迁移、侵袭及凋亡的作用(
P
<
0.05);体内实验显示,沉默LncRNA FGD5-AS1表达可显著抑制胃癌移植瘤小鼠肿瘤的生长(
P
<
0.05);RNA pull-down实验、双荧光素酶报告基因实验证实LncRNA FGD5-AS1、E2F1与miR-302b-3p存在靶向调控关系。
结论
2
LncRNA FGD5-AS1在胃癌细胞中上调表达,沉默LncRNA FGD5-AS1表达可通过调节miR-302b-3p/E2F1轴,抑制胃癌恶性进展。
Objective
2
To explore the effects of long non coding RNA FGD5-AS1 (LncRNA FGD5-AS1) on the migration and invasion of gastric cancer cells by regulating the microRNA-302b-3p (miR-302b-3p)/E2F transcription factor 1 (E2F1) axis.
Methods
2
Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of LncRNA FGD5-AS1
miR-302b-3p
and E2F1 in gastric cancer cell lines (SGC-7901
MKN-45
HGC-27
AGS
BGC-823) and human gastric epithelial cell line GES-1
in order to screen for the best intervention cells. Gastric cancer cells were separated into control group (NC group)
sh-NC group
sh-FGD5-AS1 group
sh-FGD5-AS1+anti-miR-NC group
and sh-FGD5-AS1+anti-miR-302b-3p group. qRT-PCR was performed to detect the expression of LncRNA FGD5-AS1
miR-302b-3p
and E2F1 in the cells. MTT assay and flow cytometry were applied to measure cell proliferation and apoptosis
respectively. Scratch and Transwell assays were carried out to measure cell migration and invasion
respectively. Western blotting was carried out to measure the protein levels of E2F1
Ki-67
Bax and Bcl-2. Nude mouse model of transplantable subcutaneous tumor was established to verify the effect of LncRNA FGD5-AS1 on the growth of gastric cancer transplant tumors. Dual luciferase reporter gene and RNA pull-down assays were used to detect the targeting relationship of LncRNA FGD5-AS1 and E2F1 with miR-302b-3p.
Results
2
Compared with the GES-1 cells
the gastric cancer cell lines SGC-7901
MKN-45
HGC-27
AGS and BGC-823 exhibited significantly increase
d mRNA levels of LncRNA FGD5-AS1 and E2F1
while decreased level of miR-302b-3p (
P<
0.05). AGS cells were finally selected for the following experiments. Silencing LncRNA FGD5-AS1 prominently up-regulated miR-302b-3p
down-regulated E2F1
and inhibited cell proliferation
migration
and invasion
and promoted cell apoptosis in gastric cancer AGS cells (
P<
0.05). Inhibition of miR-302b-3p partially weakened the effects of silencing LncRNA FGD5-AS1 on the proliferation
migration
invasion
and apoptosis of gastric cancer cells (
P<
0.05).
In vivo
experiments showed that silencing LncRNA FGD5-AS1 could prominently inhibit the growth of transplanted tumors in mice (
P<
0.05). RNA pull-down and dual luciferase reporter gene assays confirmed the targeted regulatory relationship of LncRNA FGD5-AS1 and E2F1 with miR-302b-3p.
Conclusion
2
LncRNA FGD5-AS1 is up-regulated in gastric cancer cells
and its silencing can inhibit the malignant progression of gastric cancer by regulating the miR-302b-3p/E2F1 axis.
王斌 , 王涛 . 胃癌的科学预防、早期诊断与精准治疗 [J]. 陆军军医大学学报 , 2025 , 47 ( 5 ): 385 - 395 . DOI: 10.16016/j.2097-0927.202501072 http://dx.doi.org/10.16016/j.2097-0927.202501072 .
WANG B , WANG T . Effective prevention, early diagnosis and precise treatment of gastric cancer [J]. J Army Med Univ , 2025 , 47 ( 5 ): 385 - 395 . DOI: 10.16016/j.2097-0927.202501072 http://dx.doi.org/10.16016/j.2097-0927.202501072 .
MATSUOKA T , YASHIRO M . Bioinformatics analysis and validation of potential markers associated with prediction and prognosis of gastric cancer [J]. Int J Mol Sci , 2024 , 25 ( 11 ): 5880 . DOI: 10.3390/ijms25115880 http://dx.doi.org/10.3390/ijms25115880 .
SALEH R O , AL-HAWARY S I S , HAMMOUD A , et al . The long non-coding RNAs (lncRNA) in the pathogenesis of gastric cancer cells: molecular mechanisms and involvement miRNAs [J]. Mol Biol Rep , 2024 , 51 ( 1 ): 615 . DOI: 10.1007/s11033-024-09546-x http://dx.doi.org/10.1007/s11033-024-09546-x .
NASERI B , FARSAD-AKHTAR N , MARDI A , et al . lncRNA PVT1 silencing inhibits gastric cancer cells' progression via enhancing chemosensitivity to paclitaxel [J]. Gene , 2025 , 932 : 148900 . DOI: 10.1016/j.gene. 2024. 148900 http://dx.doi.org/10.1016/j.gene.2024.148900 .
FENG L M , ZHENG H , ZHANG H P , et al . LncRNA FGD5-AS1 drives the malignant development of gastric cancer by negatively interacting with FZD3 [J]. Pol J Pathol , 2022 , 73 ( 1 ): 72 - 79 . DOI: 10.5114/pjp.2022.117179 http://dx.doi.org/10.5114/pjp.2022.117179 .
ZHANG W T , ZHANG J J , SHAO Q , et al . FGD5-AS1 is an oncogenic lncRNA in pancreatic cancer and regulates the Wnt/β-catenin signaling pathway via miR-577 [J]. Oncol Rep , 2022 , 47 ( 1 ): 21 . DOI: 10.3892/or.2021.8232 http://dx.doi.org/10.3892/or.2021.8232 .
GUO B , ZHAO Z H , WANG Z , et al . microRNA-302b-3p suppresses cell proliferation through AKT pathway by targeting IGF-1R in human gastric cancer [J]. Cell Physiol Biochem , 2017 , 42 ( 4 ): 1701 - 1711 . DOI: 10.1159/000479419 http://dx.doi.org/10.1159/000479419 .
王建新 , 王琳茜 , 朱波 , 等 . 人参皂苷Rg3通过调控E2F1对人胃癌SGC-7901细胞生物行为学的影响 [J]. 中国药理学通报 , 2024 , 40 ( 5 ): 853 - 858 .
WANG J X , WANG L Q , ZHU B , et al . Effects of ginsenoside Rg3 on biobehavior of human gastric cancer SGC-7901 cells by regulating E2F1 [J]. Chin Pharmacol Bull , 2024 , 40 ( 5 ): 853 - 858 .
LIN X L , HAN T , XIA Q , et al . CHPF promotes gastric cancer tumorigenesis through the activation of E2F1 [J]. Cell Death Dis , 2021 , 12 ( 10 ): 876 . DOI: 10.1038/s41419-021-04148-y http://dx.doi.org/10.1038/s41419-021-04148-y .
ACS M , PISO P , GLOCKZIN G . Peritoneal metastatic gastric cancer: local treatment options and recommendations [J]. Curr Oncol , 2024 , 31 ( 3 ): 1445 - 1459 . DOI: 10.3390/curroncol31030109 http://dx.doi.org/10.3390/curroncol31030109 .
LIU C C , SHEN A W , SONG J Q , et al . LncRNA-CCAT5-mediated crosstalk between Wnt/β-Catenin and STAT3 signaling suggests novel therapeutic approaches for metastatic gastric cancer with high Wnt activity [J]. Cancer Commun (Lond) , 2024 , 44 ( 1 ): 76 - 100 . DOI: 10.1002/cac2.12507 http://dx.doi.org/10.1002/cac2.12507 .
MA L , LIU W H , WANG X , et al . Mechanism of RBM15 in the malignant proliferation of colorectal cancer cells through regulating the stability of LncRNA FGD5-AS1 via m6A modification [J]. Exp Cell Res , 2025 , 444 ( 2 ): 114384 . DOI: 10.1016/j.yexcr.2024.114384 http://dx.doi.org/10.1016/j.yexcr.2024.114384 .
QI W X , LIU Q , FU W J , et al . BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer [J]. Sci Rep , 2023 , 13 ( 1 ): 16400 . DOI: 10.1038/s41598-023-43577-x http://dx.doi.org/10.1038/s41598-023-43577-x .
刘晶 , 张国民 , 李强 , 等 . LncRNA FGD5-AS1调节miR-129-5p/CDK6轴对膀胱癌细胞恶性生物行为的影响 [J]. 2023 ( 12 ): 1079 - 1085 . DOI: 10.3969/j.issn.1009-8291.2023.12.015 http://dx.doi.org/10.3969/j.issn.1009-8291.2023.12.015 .
LIU J , ZHANG G M , LI Q , et al . Effect of LncRNA FGD5-AS1 on malignant biological behavior of bladder cancer cells by regulating miR-129-5p/CDK6 axis [J]. J Modern Urol , 2023 ( 12 ): 1079 - 1085 . DOI: 10.3969/j.issn.1009-8291.2023.12.015 http://dx.doi.org/10.3969/j.issn.1009-8291.2023.12.015 .
XIA Z Y , ZHANG L P , ZHOU H G , et al . LncRNA-FGD5-AS1 promotes 5-Fu resistance of cervical cancer cells through modulating the miR-130a-3p-YTHDF2 axis [J]. J Chemother , 2025 , 37 ( 8 ): 710 - 722 . DOI: 10.1080/1120009x.2024.2436803 http://dx.doi.org/10.1080/1120009x.2024.2436803 .
QIN S S , LIU Y , ZHANG X G , et al . lncRNA FGD5-AS1 is required for gastric cancer proliferation by inhibiting cell senescence and ROS production via stabilizing YBX1 [J]. J Exp Clin Cancer Res , 2024 , 43 ( 1 ): 188 . DOI: 10.1186/s13046-024-03103-x http://dx.doi.org/10.1186/s13046-024-03103-x .
LIU L , ZHANG C , WANG J Z , et al . A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer [J]. BMC Cancer , 2021 , 21 ( 1 ): 453 . DOI: 10.1186/s12885-021-08192-x http://dx.doi.org/10.1186/s12885-021-08192-x .
XU H , MIAO X , LI X , et al . LncRNA SNHG16 contributes to tumor progression via the miR-302b-3p/SLC2A4 axis in pancreatic adenocarcinoma [J]. Cancer Cell Int , 2021 , 21 ( 1 ): 51 . DOI: 10.1186/s12935-020-01715-9 http://dx.doi.org/10.1186/s12935-020-01715-9 .
LI Y , TANG B J , LYU K X , et al . Low expression of lncRNA SBF2-AS1 regulates the miR-302b-3p/TGFBR2 axis, promoting metastasis in laryngeal cancer [J]. Mol Carcinog , 2022 , 61 ( 1 ): 45 - 58 . DOI: 10.1002/mc.23358 http://dx.doi.org/10.1002/mc.23358 .
WANG D , JIANG X H , LIU Y , et al . Circular RNA circ_HN1 facilitates gastric cancer progression through modulation of the miR-302b-3p/ROCK2 axis [J]. Mol Cell Biochem , 2021 , 476 ( 1 ): 199 - 212 . DOI: 10.1007/s11010-020-03897-2 http://dx.doi.org/10.1007/s11010-020-03897-2 .
ZHOU F F , DENG Z , SHEN D X , et al . DLGAP5 triggers proliferation and metastasis of bladder cancer by stabilizing E2F1 via USP11 [J]. Oncogene , 2024 , 43 ( 8 ): 594 - 607 . DOI: 10.1038/s41388-023-02932-y http://dx.doi.org/10.1038/s41388-023-02932-y .
XU T , XIONG M Q , HONG Q W , et al . Hsa_circ_0007990 promotes breast cancer growth via inhibiting YBX1 protein degradation to activate E2F1 transcription [J]. Cell Death Dis , 2024 , 15 ( 2 ): 153 . DOI: 10.1038/s41419-024-06527-7 http://dx.doi.org/10.1038/s41419-024-06527-7 .
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621