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中华普通外科学文献(电子版) ›› 2021, Vol. 15 ›› Issue (04) : 288 -292. doi: 10.3877/cma.j.issn.1674-0793.2021.04.010

论著

miR-877-3p靶向人类表皮生长因子受体2/ PI3K/AKT信号通路介导乳腺癌增殖、迁移和侵袭
李新1, 田蜜2, 何莉莉1,()   
  1. 1. 448000 荆门市第二人民医院甲乳外科
    2. 448000 荆门市公安局法医鉴定中心
  • 收稿日期:2020-11-15 出版日期:2021-08-03
  • 通信作者: 何莉莉
  • 基金资助:
    湖北省荆门市科技项目(2020YFYB012)

miR-877-3p regulating the proliferation, migration and invasion of breast cancer cells via HER-2/PI3K/AKT signaling pathway

Xin Li1, Mi Tian2, Lili He1,()   

  1. 1. Department of Thyroid and Breast Surgery, Jingmen No.2 People’s Hospital, Jingmen 448000, China
    2. Forensic Identification Center of Jingmen Public Security Bureau, Jingmen 448000, China
  • Received:2020-11-15 Published:2021-08-03
  • Corresponding author: Lili He
引用本文:

李新, 田蜜, 何莉莉. miR-877-3p靶向人类表皮生长因子受体2/ PI3K/AKT信号通路介导乳腺癌增殖、迁移和侵袭[J]. 中华普通外科学文献(电子版), 2021, 15(04): 288-292.

Xin Li, Mi Tian, Lili He. miR-877-3p regulating the proliferation, migration and invasion of breast cancer cells via HER-2/PI3K/AKT signaling pathway[J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(04): 288-292.

目的

研究miR-877-3p靶向人类表皮生长因子受体2(HER-2)并调节其下游PI3K/AKT信号通路介导乳腺癌的增殖、迁移、侵袭和愈合功能的分子机制。

方法

通过qPCR和Western blotting法评估miR-877-3p和HER-2在正常乳腺上皮细胞和乳腺癌细胞中的表达。CCK-8、Transwell和愈合实验分析miR-877-3p在乳腺癌细胞中的增殖、迁移、侵袭和愈合功能,荧光素酶报告基因实验检测miR-877-3p和HER-2的靶向关系。Western blotting实验评估miR-877-3p靶向HER-2及其下游PI3K/AKT信号通路蛋白的表达水平。

结果

miR-877-3p的表达与乳腺癌细胞中HER-2呈负相关;miR-877-3p抑制乳腺癌细胞增殖、迁移、侵袭和愈合功能;HER-2是miR-877-3p的直接靶标;miR-877-3p靶向HER-2调控PI3K/AKT信号通路。

结论

miR-877-3p靶向HER-2/PI3K/AKT信号通路介导乳腺癌增殖、迁移和侵袭。

Objective

To explore the molecular mechanism of miR-877-3p targeting HER-2 and regulating its downstream PI3K/AKT signaling pathway to mediate the proliferation, migration, invasion and healing functions of breast cancer.

Methods

The expression of miR-877-3p and HER-2 was evaluated in normal breast epithelial cells and breast cancer cells using qPCR and Western blotting assay. Furthermore, the proliferation, migration, invasion and healing functions of miR-877-3p were analyzed in breast cancer cells by CCK-8, Transwell and healing experiments. Additionally, the targeting relationship betweenmiR-877-3p and HER-2 was detected by luciferase reporter gene experiment. The expression levels of miR-877-3p targeting HER-2 and its downstream PI3K/AKT signaling pathway proteins were evaluated by Western blotting assay.

Results

miR-877-3p expression was negatively correlated with HER-2 in breast cancer cells. The proliferation, migration, invasion and healing functions were supressed by miR-877-3p in breast cancer cell. HER-2 was a direct target of miR-887-3p. miR-877-3p targeted HER-2 to regulate PI3K/AKT signaling pathway.

Conclusion

miR-877-3p targets HER-2/PI3K/AKT signaling pathway to mediate the proliferation, migration and invasion of breast cancer.

图1 miR-877-3p和HER-2在乳腺癌细胞中的表达 A、B为通过qPCR检测4种不同细胞类型中miR-877-3p和HER-2的表达,以正常乳腺细胞(NC)为标准化;C为通过Western blotting检测4种不同细胞类型中HER-2的表达,以GAPDH为内参对照。* P<0.05,** P<0.01
图2 miR-877-3p抑制乳腺癌细胞增殖 A为通过qPCR检测乳腺癌细胞中miR-877-3p的表达,mimic-NC为对照组;B为通过CCK-8实验miR-877-3p对乳腺癌细胞增殖的作用,过表达miR-877-3p后分别检测12、24、48和72 h的吸光度值(A450)。* P<0.05,** P<0.01,*** P<0.001
图3 miR-877-3p抑制乳腺癌细胞迁移、侵袭和愈合 A、B为将miR-877-3p转入乳腺癌细胞中,24 h后用Transwell和结晶紫染色的方法检测细胞的迁移和侵袭能力;C、D为将miR-877-3p转入乳腺癌细胞中,分别在24、48 h评估细胞的愈合能力。放大倍数为200×,*P<0.05,**P<0.01
图4 HER-2是miR-877-3p的直接靶标 A根据TargetScan和miRDB等生物信息学分析的miR-877-3p可能与HER-2结合的3’UTR序列及其突变(MUT)序列;B将构建好的HER-2 WT和HER-2 MUT的荧光素酶质粒分别与miR-877-3p mimic共转入乳腺癌细胞中,24 h后用酶标仪检测荧光素酶的活性。* P<0.05
图5 miR-877-3p靶向调控HER-2/PI3K/AKT信号通路 A将miR-877-3p mimic转入乳腺癌细胞中,B为24 h后通过Western blotting检测HER-2、PI3K、AKT的蛋白质表达水平,以GAPDH为内参对照。*P<0.05,** P<0.01
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