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[1]贺海发a,万里新b,李凯,等.阿帕替尼调控miR-129-5p/PBX3轴抑制食管癌细胞恶性生物学行为的研究[J].天津医科大学学报,2025,31(02):126-133.
　HE Haifaa,WAN Lixinb,LI Kai,et al.Apatinib inhibits malignant biological behavior of esophageal cancer cells by modulation of miR-129-5p/PBX3 axis[J].Journal of Tianjin Medical University,2025,31(02):126-133.
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阿帕替尼调控miR-129-5p/PBX3轴抑制食管癌细胞恶性生物学行为的研究(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
31卷
期数:
2025年02期
页码:
126-133
栏目:
基础医学
出版日期:
2025-03-20

文章信息/Info

Title:
Apatinib inhibits malignant biological behavior of esophageal cancer cells by modulation of miR-129-5p/PBX3 axis
文章编号:
1006-8147(2025)02-0126-08
作者:
贺海发1a; 万里新1b; 李凯2; 李寅3; 王媛1c; 杜云辉1b
（1.南阳市中心医院a病理科，b肿瘤内科，c消化道肿瘤内科，南阳473000；2.南阳理工学院张仲景国医国药学院，南阳473004；3.南阳医学高等专科学校病理学教研室，南阳473004）
Author(s):
HE Haifa1a; WAN Lixin1b; LI Kai2; LI Yin3; WANG Yuan1c; DU Yunhui1b
（1.a Department of Pathology，b Department of Oncology，c Department of Gastrointestinal Oncology，Nanyang Central Hospital，Nanyang 473000，China；2.Zhang Zhongjing Institute of Chinese Medicine，Nanyang Institute of Technology，Nanyang 473004，China；3.Department of Pathology，Nanyang Medical College，Nanyang 473004，China）
关键词:
食管癌; 阿帕替尼; 前B细胞白血病同源盒基因3; Janus激酶2; 信号转导及转录激活因子3
Keywords:
esophagus cancer; apatinib; pre-B-cell leukemia homeobox gene 3; Janus kinase 2; signal transducer and activator of transcription 3
分类号:
R735.1
DOI:
-
文献标志码:
A
摘要:
目的：探讨阿帕替尼（Apatinib）通过微小RNA（miR）-129-5p调控前B细胞白血病同源盒基因3（PBX3）对食管癌细胞恶性生物学行为的影响。方法：CCK-8法和划痕实验检测不同浓度Apatinib处理后KYSE450食管癌细胞的增殖、迁移能力；将KYSE450细胞分为KYSE450组、Apatinib-H组、Apatinib-H+miR-129-5p mimic组、Apatinib-H+miR-129-5p mimic+oe-PBX3组，qRT-PCR及免疫荧光检测miR-129-5p、PBX3表达水平，EdU、Transwell和TUNEL法检测细胞增殖、侵袭和凋亡情况，免疫印迹法检测Janus激酶2（JAK2）/信号转导及转录激活因子3（STAT3）信号通路相关蛋白水平。将293T人胚肾细胞分为293T+mimic NC组、293T+miR-129-5p mimic组，双荧光素酶报告基因实验验证miR-129-5p/PBX3的靶向关系。结果：20、40、60 μmol/L的Apatinib均能抑制KYSE450细胞的增殖（t=4.416、11.331、13.121，均P<0.01）、迁移（t=2.277、4.286、6.722，均P<0.05）；miR-129-5p与PBX3存在靶向关系；与KYSE450组相比，Apatinib-H组miR-129-5p mRNA水平升高（t=6.327，P<0.01），PBX3 mRNA及蛋白水平降低（t=6.098、10.403，均P<0.05）；与Apatinib-H组相比，加入miR-129-5p模拟物可使KYSE450细胞的增殖率、侵袭个数及JAK2/STAT3通路关键蛋白水平降低，凋亡率升高（t=3.112、2.428、4.726、3.619、4.258，均P<0.05），过表达PBX3可逆转上述变化（t=3.698、3.199、4.082、3.563、5.840，均P<0.01）。结论：阿帕替尼可能通过上调miR-129-5p而靶向下调PBX3，抑制肿瘤细胞的恶性生物学行为。
Abstract:
Objective：To investigate the effect of Apatinib on the malignant biological behavior of esophageal carcinoma cells by regulating the pre-B-cell leukemia homeobox gene 3（PBX3） through microRNA（miR） -129-5p. Methods：The CCK-8 assay and scratch assay were used to detect the proliferation and migration ability of KYSE450 esophageal cancer cells after treatment with different concentrations of Apatinib；KYSE450 cells were divided into the KYSE450 group，the Apatinib-H group，the Apatinib-H+miR-129-5p mimic group，the Apatinib-H+miR-129- 5p mimic+oe-PBX3 group. The expression levels of miR-129-5p and PBX3 were detected by qRT-PCR and immunofluorescence.EdU，Transwell and TUNEL methods were used to detect cell proliferation，invasion and apoptosis，and the levels of proteins associated with the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway were detected by Western blotting. The 293T cells were divided into 293T+mimic NC group and 293T+miR-129-5p mimic group，and Dual luciferase reporter gene assay was used to verifiy the miR-129-5p/PBX3 targeting relationship. Results：20，40，and 60 μmol/L of Apatinib inhibited the proliferation （t=4.416，11.331，13.121，all P<0.01） and migration （t=2.277，4.286，6.722，all P<0.05） of the KYSE450 cells；there was a targeting relationship between miR-129-5p and PBX3. Compared with the KYSE450 group，miR-129-5p mRNA levels were increased （t=6.327，P<0.01），PBX3 mRNA and protein levels were decreased （t=6.098，10.403，both P<0.05）in the Apatinib-H group. Compared with Apatinib-H group，the addition of miR-129-5p mimics reduced the proliferation rate，the number of invasion and the level of key proteins of JAK2/STAT3 pathway，and increased the apoptosis rate of KYSE450 cells（t=3.112，2.428， 4.726，3.619，4.258，all P<0.05），and overexpression of PBX3 reversed the above changes （t=3.698，3.199，4.082，3.563，5.840， all P<0.01）. Conclusion：Apatinib may target down-regulate PBX3 by up-regulating miR-129-5p，and inhibit the malignant biological behavior of tumor cells.

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备注/Memo

备注/Memo:
基金项目:河南省科技厅项目（242102310537）
作者简介:贺海发（1983-），男，主治医师，硕士，研究方向：消化道肿瘤的相关研究；通信作者：万里新，E-mail：nanyang1967@163.com。
更新日期/Last Update: 2025-03-20