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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2023, Vol. 13 ›› Issue (05) : 277 -287. doi: 10.3877/cma.j.issn.2095-1221.2023.05.004

论著

miR-138-5p调节HIF-1α/Notch1轴对滋养层细胞侵袭和血管生成的影响
刘佳†(), 付丽, 杨月美   
  1. 430100　武汉，武汉市蔡甸区人民医院产科
  • 收稿日期:2023-05-18 出版日期:2023-10-01
  • 通信作者: 刘佳

Impacts of miR-138-5p on trophoblast invasion and angiogenesis by regulating the HIF-1α/Notch1 axis

Jia Liu†(), Li Fu, Yuemei Yang   

  1. Department of Obstetrics, Caidian District People's Hospital, Wuhan, Hubei, 430100
  • Received:2023-05-18 Published:2023-10-01
  • Corresponding author: Jia Liu
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引用本文：

刘佳, 付丽, 杨月美. miR-138-5p调节HIF-1α/Notch1轴对滋养层细胞侵袭和血管生成的影响[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(05): 277-287.

Jia Liu, Li Fu, Yuemei Yang. Impacts of miR-138-5p on trophoblast invasion and angiogenesis by regulating the HIF-1α/Notch1 axis[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(05): 277-287.

目的

探究微小RNA-138-5p （miR-138-5p）对滋养层细胞侵袭和血管生成的影响，并进一步研究其对缺氧诱导因子1α （HIF-1α）/Notch1轴的调节作用。

方法

体外培养人滋养层细胞系HTR-8/SVneo，分别转染mimics NC （miR-NC）、miR-138-5p模拟物（miR-138-5p mimics）、抑制剂阴性对照（inhibitor NC）、miR-138-5p抑制剂（miR-138-5p inhibitor）、pcDNA-NC （oe-NC）、pcDNA-HIF-1α （oe-HIF-1α）、miR-138-5p模拟物与pcDNA-NC （miR-138-5p mimics+oe-NC）、miR-138-5p模拟物与pcDNA-HIF-1α （miR-138-5p mimics+ oe-HIF-1α）。转染后继续培养48 h，采用MTT法和克隆形成实验检测细胞增殖情况；Transwell法检测细胞侵袭情况；流式细胞术检测细胞凋亡率；管形成实验检测血管生成情况；qRT-PCR法检测细胞中miR-138-5p表达；Western blot法检测细胞中HIF-1α、Notch1、MMP-2、MMP-9、VEGF蛋白表达。双荧光素酶报告基因实验验证miR-138-5p与HIF-1α的靶向关系。两组间比较采用独立样本t检验，多组间比较采用单因素方差分析和SNK-q检验。

结果

过表达miR-138-5p后细胞存活率、克隆形成数、侵袭个数、管形成数量（33.15 ± 3.85比64.53 ± 4.12）下降，细胞凋亡率升高，HIF-1α、Notch1、MMP-2、MMP-9、VEGF蛋白表达（0.26 ± 0.04比0.46 ± 0.05）降低（P均< 0.05）；抑制miR-138-5p表达上述指标变化相反。双荧光素酶报告基因实验结果显示miR-138-5p与HIF-1α存在靶向关系。过表达HIF-1α后细胞存活率、克隆形成数、侵袭个数、管形成数量升高，细胞凋亡率降低，Notch1及MMP-2、MMP-9、VEGF蛋白表达升高（P均< 0.05）；过表达HIF-1α可逆转过表达miR-138-5p对上述指标变化的影响。

结论

miR-138-5p可能通过靶向负调控HIF-1α/Notch1轴对滋养层细胞增殖、侵袭能力与血管生成产生影响。

关键词: 微小RNA-138-5p, 缺氧诱导因子1α, Notch1, 先兆子痫, 侵袭, 血管生成
Objective

To explore the effects of microRNA-138-5p (miR-138-5p) on trophoblast invasion and angiogenesis, and to further study its regulatory impact on hypoxia-inducible factor 1α (HIF-1α) /Notch1 axis.

Methods

Human trophoblast cell line HTR-8/SVneo cultured in vitro were transfected with mimics NC (miR-NC) , miR-138-5p mimics, inhibitor negative control (inhibitor NC) , miR-138-5p inhibitor (miR-138-5p inhibitor) , pcDNA-NC (oe-NC) , pcDNA-HIF-1α (oe-HIF-1α) , miR-138-5p mimics and pcDNA-NC (miR-138-5p mimics+oe-NC) , miR-138-5p mimics and pcDNA-HIF-1α (miR-138-5p mimics +oe-HIF-1α) , respectively. After transfection, the cells were cultured for 48 h, and the proliferation was detected by MTT assay and clone formation assay; cell invasion was detected by Transwell; the apoptosis rate was detected by flow cytometry; angiogenesis was detected by tube formation test; qRT-PCR detected the expression of miR-138-5p; Western Blot detected the expressions of HIF-1α, Notch1, MMP-2, MMP-9 and VEGF; dual luciferase reporter assay verified the targeting relationship between miR-138-5p and HIF-1α.

Results

The cell survival rate, the number of clone formations, the number of invasion and the number of tubes formed were significantly decreased after overexpression of miR-138-5p; In contrast, the apoptosis rate was significantly increased, and the protein expressions of HIF-1α, Notch1, MMP-2, MMP-9 and VEGF were significantly decreased (all P < 0.05) ; inhibition of miR-138-5p expression changed the above indicators in the opposite direction. The results of the dual-luciferase reporter gene assay showed that miR-138-5p had a targeting relationship with HIF-1α. After HIF-1α overexpression, the cell survival rate, the number of clone formation, the number of invasions and the number of tubes formed were significantly increased, the cell apoptosis rate was significantly decreased, and the expressions of Notch1, MMP-2, MMP-9 and VEGF were significantly increased (all P < 0.05) . Up-regulation of HIF-1α reversed the influence of miR-138-5p overexpression on the changes of the above indexes.

Conclusion

miR-138-5p may affect trophoblast cell proliferation, invasion ability and angiogenesis by targeting and negatively regulating the HIF-1α/Notch1 axis.

Key words: microRNA-138-5p, Hypoxia-inducible factor 1α, Notch1, Preeclampsia, Invasion, Angiogenesis
表1 引物序列信息
基因 序列（5'→3'） 预期扩增产物长度（bp）
miR-138-5p 上游TGTGAATCAGGCCGTTGC 76
  下游GCCCTGGTGTTGTGAAGTAG  
U6（内参） 上游CTCGCTTCGGCAGCACA 98
  下游AACGCTTCACGAATTTGCGT  
表2 HTR-8/Svneo细胞中miR-138-5p表达的比较（ ± s）
分组 实验次数 miR-138-5p
对照 3 1.06 ± 0.10
miR-NC 3 1.01 ± 0.13
miR-138-5p mimics 3 1.96 ± 0.16ab
inhibitor NC 3 1.03 ± 0.12
miR-138-5p inhibitor 3 0.40 ± 0.07ac
F值   64.966
P值   < 0.001
图1 正常视野下观察滋养层细胞克隆形成情况
图2 光学显微镜下观察滋养层细胞侵袭情况（结晶紫染色，×200）注：a图为对照；b图为miR-NC；c图为miR-138-5p mimics；d图为inhibitor NC；e图为miR-138-5p inhibitor
图3 滋养层细胞凋亡情况注：a图为对照；b图为miR-NC；c图为miR-138-5p mimics；d图为inhibitor NC；e图为miR-138-5p inhibitor
图4 滋养层细胞血管生成情况注：a图为对照；b图为miR-NC；c图为miR-138-5p mimics；d图为inhibitor NC；e图为miR-138-5p inhibitor
表3 HTR-8/Svneo细胞存活率、克隆形成数、侵袭个数、凋亡率和管形成数量的比较（ ± s）
分组 实验次数 存活率（%） 克隆形成数 侵袭个数 凋亡率（%） 管形成数量
对照 3 98.36 ± 5.41 89.51 ± 4.56 67.43 ± 5.11 8.27 ± 1.12 64.53 ± 4.12
miR-NC 3 98.71 ± 4.84 87.98 ± 4.64 65.19 ± 5.43 8.56 ± 0.95 63.48 ± 4.09
miR-138-5p mimics 3 39.46 ± 2.88ab 38.74 ± 3.49ab 36.71 ± 4.78ab 24.62 ± 2.27ab 33.15 ± 3.85ab
inhibitor NC 3 97.74 ± 4.28 86.67 ± 5.38 64.62 ± 6.72 8.41 ± 1.06 62.98 ± 3.79
miR-138-5p inhibitor 3 142.59 ± 6.47ac 181.62 ± 13.14ac 153.47 ± 12.86ac 3.85 ± 0.59ac 132.46 ± 10.12ac
F值   166.548 158.118 101.919 109.495 121.871
P值   <0.001 < 0.001 < 0.001 < 0.001 < 0.001
图5 Western blot检测滋养层细胞中HIF-1α、MMP-2、MMP-9、VEGF蛋白表达注：1为对照；2为miR-NC；3为miR-138-5p mimics；4为inhibitor NC；5为miR-138-5p inhibitor
表4 滋养层细胞中HIF-1α、Notch1、MMP-2、MMP-9和VEGF蛋白表达的比较（ ± s）
分组 实验次数 HIF-1α Notch1 MMP-2 MMP-9 VEGF
对照 3 0.50 ± 0.06 0.26 ± 0.03 0.35 ± 0.04 0.43 ± 0.05 0.46 ± 0.05
miR-NC 3 0.51 ± 0.07 0.28 ± 0.04 0.33 ± 0.03 0.45 ± 0.04 0.47 ± 0.06
miR-138-5p mimics 3 0.28 ± 0.04ab 0.13 ± 0.02ab 0.20 ± 0.03ab 0.25 ± 0.03ab 0.26 ± 0.04ab
inhibitor NC 3 0.47 ± 0.05 0.29 ± 0.04 0.36 ± 0.05 0.41 ± 0.04 0.45 ± 0.05
miR-138-5p inhibitor 3 0.93 ± 0.10ac 0.61 ± 0.06ac 0.75 ± 0.06ac 0.82 ± 0.07ac 0.80 ± 0.09ac
F值   37.679 58.389 67.689 57.548 31.123
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
图6 生物信息学网站预测miR-138-5p与HIF-1α结合位点
表5 双荧光素酶报告基因检测结果（ ± s）
因素 实验次数 因素
HIF-1α-wt HIF-1α-mut
NC 3 1.02 ± 0.09 1.03 ± 0.10
miR-138-5p 3 0.32 ± 0.03 0.97 ± 0.09
t值   12.780 0.772
P值   < 0.001 0.483
图7 正常视野及光学显微镜下观察滋养层细胞克隆生成和侵袭情况注：a，d图为对照；b，e图为oe-NC；c，f图为oe-HIF-1α，d ~ f图为结晶紫染色，×200
图8 各组滋养层细胞凋亡情况注：a为对照；b为oe-NC；c为oe-HIF-1α
图9 各组滋养层细胞血管生成情况注：a为对照；b为oe-NC；c为oe-HIF-1α
图10 Western blot检测滋养层细胞中HIF-1α、MMP-2、MMP-9、VEGF蛋白表达
表6 过表达HIF-1α的HTR-8/Svneo细胞存活率、克隆形成数、侵袭个数、凋亡率和管形成数量以及HIF-1α、Notch1、MMP-2、MMP-9、VEGF蛋白表达比较（ ± s）
分组 实验次数 存活率（%） 克隆形成数 侵袭个数 凋亡率（%） 管形成数量
对照 3 98.50 ± 5.69 88.45 ± 4.35 66.5 ± 5.44 8.40 ± 1.05 65.12 ± 3.98
oe-NC 3 98.64 ± 5.75 87.93 ± 4.41 65.9 ± 5.08 8.45 ± 0.97 64.69 ± 4.06
oe-HIF-1α 3 137.20 ± 7.36ab 143.25 ± 10.06ab 124.8 ± 9.32ab 4.12 ± 0.66ab 112.15 ± 8.43ab
F值   37.429 65.165 72.458 22.430 64.772
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
分组 实验次数 HIF-1α Notch1 MMP-2 MMP-9 VEGF
对照 3 0.50 ± 0.06 0.27 ± 0.03 0.34 ± 0.04 0.47 ± 0.05 0.43 ± 0.06
oe-NC 3 0.48 ± 0.05 0.25 ± 0.04 0.33 ± 0.05 0.49 ± 0.06 0.40 ± 0.05
oe-HIF-1α 3 0.95 ± 0.09ab 0.70 ± 0.08ab 0.61 ± 0.07ab 0.78 ± 0.09ab 0.82 ± 0.08ab
F值   44.768 65.360 25.233 19.077 39.528
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
图11 正常视野和光学显微镜下观察各组滋养层细胞克隆生成和侵袭情况注：a，c图为miR-138-5p mimics+oe-NC；b，d图为miR-138-5p mimics+oe-HIF-1α，结晶紫染色，×200
图12 各组滋养层细胞凋亡和细胞血管生成情况注：a，c图为miR-138-5p mimics+oe-NC；b，d图为miR-138-5p mimics+oe-HIF-1α
图13 Western blot检测滋养层细胞中HIF-1α、Notch1、MMP-2、MMP-9、VEGF蛋白表达
表7 过表达miR-138-5p和HIF-1α的HTR-8/Svneo细胞存活率、克隆形成数、侵袭个数、凋亡率和管形成数量以及HIF-1α、MMP-2、MMP-9、VEGF蛋白表达比较（ ± s）
分组 实验次数 存活率（%） 克隆形成数 侵袭个数 凋亡率（%） 管形成数量
miR-138-5p mimics+oe-NC 3 38.75 ± 3.60 38.65 ± 3.43 35.8 ± 4.73 24.56 ± 2.15 32.98 ± 3.74
miR-138-5p mimics+oe-HIF-1α 3 85.44 ± 5.12 79.86 ± 4.12 52.9 ± 5.51 13.27 ± 1.48 50.03 ± 3.51
t值   12.921 13.315 3.439 7.492 5.758
P值   < 0.001 < 0.001 0.026 0.002 0.005
分组 实验次数 HIF-1α Notch1 MMP-2 MMP-9 VEGF
miR-138-5p mimics+oe-NC 3 0.31 ± 0.04 0.15 ± 0.02 0.18 ± 0.03 0.23 ± 0.04 0.27 ± 0.04
miR-138-5p mimics+oe-HIF-1α 3 0.57 ± 0.06 0.31 ± 0.03 0.32 ± 0.04 0.38 ± 0.05 0.40 ± 0.05
t值   6.245 7.686 4.850 4.058 3.517
P值   0.003 0.002 0.008 0.015 0.025
1
张静, 王夏, 姜虹, 等. 孕中期先兆子痫患者血清瘦素和脂联素及趋化因子水平与病情严重程度相关性[J]. 中华实用诊断与治疗杂志, 2022, 36(9):928-931.
2
Emeruwa UN, Gyamfi-Bannerman C, Laurent LC. Biomarkers and the risk of preeclampsia[J]. JAMA, 2023, 329(7):539-541.
3
Liu D, Gao Q, Wang Y, et al. Placental dysfunction: The core mechanism for poor neurodevelopmental outcomes in the offspring of preeclampsia pregnancies[J]. Placenta, 2022, 126:224-232.
4
Zhou W, Wang H, Yang Y, et al. Trophoblast cell subtypes and dysfunction in the placenta of individuals with preeclampsia revealed by single-cell RNA sequencing[J]. Mol Cells, 2022, 45(5):317-328.
5
Jaszczuk I, Koczkodaj D, Kondracka A, et al. The role of miRNA-210 in pre-eclampsia development[J]. Ann Med, 2022, 54(1):1350-1356.
6
李勤, 许娟秀, 尧旋. LncRNA HIF1A-AS2通过抑制miR-138-5p促进滋养层细胞的侵袭和上皮间充质转化[J]. 第三军医大学学报, 2020, 42(22):2210-2218.
7
Wang Y, Shen Y, Liu Z, et al. Dl-NBP (Dl-3-N-Butylphthalide) treatment promotes neurological functional recovery accompanied by the upregulation of white matter integrity and HIF-1α/VEGF/Notch/Dll4 expression[J]. Front Pharmacol, 2020, 10:1595. doi: 10.3389/fphar.2019.01595.
8
Qiu TY, Huang J, Wang LP, et al. Inhibition of miR-200b promotes angiogenesis in endothelial cells by activating the notch pathway[J]. Cell J, 2021, 23(1):51-60.
9
Jing L, Ruan Z, Sun H, et al. Epithelial-mesenchymal transition induced cancer-stem-cell-like characteristics in hepatocellular carcinoma[J]. J Cell Physiol, 2019, 234(10):18448-18458.
10
Yu N, Wu JL, Xiao J, et al. HIF-1α regulates angiogenesis via Notch1/STAT3/ETBR pathway in trophoblastic cells[J]. Cell Cycle, 2019, 18(24):3502-3512.
11
Liu ZZ, Tian YF, Wu H, et al. LncRNA H19 promotes glioma angiogenesis through miR-138/HIF-1α/VEGF axis[J]. Neoplasma, 2020, 67(1):111-118.
12
Liao J, Zheng Y, Hu M, et al. Impaired sphingosine-1-phosphate synthesis induces preeclampsia by deactivating trophoblastic YAP (Yes-associated protein) through S1PR2 (sphingosine-1-phosphate receptor-2)-induced actin polymerizations[J]. Hypertension, 2022, 79(2):399-412.
13
Sammar M, Apicella C, Altevogt P, et al. Modeling preeclampsia in vitro: polymorphic variants of STOX1-A/B genes can downregulate CD24 in trophoblast cell lines[J]. Int J Mol Sci, 2022, 23(24):15927. doi: 10.3390/ijms232415927.
14
Natenzon A, McFadden P, DaSilva-Arnold SC, et al. Diminished trophoblast differentiation in early onset preeclampsia[J]. Placenta, 2022, 120:25-31.
15
周俏苗, 汪洪林, 黄海燕, 等. miR-124-3p靶向调控MAPK 14对子痫前期大鼠胎盘滋养层细胞增殖及侵袭的影响[J]. 中国比较医学杂志, 2020, 30(6):1-9.
16
高志伟. PLGF miRNA-210水平在子痫前期患者中的表达及与妊娠结局的关系[J]. 中国妇幼保健, 2023, 38(7):1287-1290.
17
Chen J, Khalil RA. Matrix metalloproteinases in normal pregnancy and preeclampsia[J]. Prog Mol Biol Transl Sci, 2017, 148:87-165.
18
Akanuma N, Hoshino I, Akutsu Y,et al. MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer[J]. Br J Cancer, 2014, 110(1):189-198.
19
Nikolov A, Popovski N. Role of gelatinases MMP-2 and MMP-9 in healthy and complicated pregnancy and their future potential as preeclampsia biomarkers[J]. Diagnostics (Basel), 2021, 11(3):480. doi: 10.3390/diagnostics11030480.
20
Yu Y, Fang L, Wang S, et al. Amphiregulin promotes trophoblast invasion and increases MMP9/TIMP1 ratio through ERK1/2 and Akt signal pathways[J]. Life Sci, 2019, 236:116899. doi: 10.1016/j.lfs.2019.116899.
21
Xiong J, Jin X, Xu K, et al. LncRNA-loc391533 is involved in the progression of preeclampsia through VEGF[J]. Ginekol Pol, 2022, 2022:1-22. doi: 10.5603/GP.a2022.0056.
22
Buijs N, Oosterink JE, Jessup M, et al. A new key player in VEGF-dependent angiogenesis in human hepatocellular carcinoma: dimethylarginine dimethylaminohydrolase 1[J]. Angiogenesis, 2017, 20(4):557-565.
23
王美玲, 刘华绪. HIF-VEGF-Notch信号通路在血管生成中的作用[J]. 中国麻风皮肤病杂志, 2021, 37(5):332-336.
24
Cheng Z, Fu J, Liu G, et al. Angiogenesis in JAK2 V617F positive myeloproliferative neoplasms and ruxolitinib decrease VEGF, HIF-1 enesis in JAK2 V617F positive cells[J]. Leuk Lymphoma, 2018, 59(1):196-203.
25
焦毅, 张雪竹. 舒肝明目汤含药血清调节HIF1α-VEGF-Notch1通路活性影响脉络膜血管新生作用的研究[J]. 天津中医药, 2017, 34(7):471-474.
26
丁君, 郑瑾, 范威. HIF-1α和Notch1在原代培养的神经元及胶质细胞的混合体系中的相互作用[J]. 神经损伤与功能重建, 2021, 16(12):695-697.
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