基础研究

LncRNA SNHG8在胎盘植入的表达及其对滋养细胞侵袭及迁移的影响

  • 高丽娜 ,
  • 刘小晖 ,
  • 张玉芳 ,
  • 刘小玲 ,
  • 何晓春 ,
  • 高晶 ,
  • 张莉 ,
  • 孙俊 ,
  • 王秀娟 ,
  • 董燕
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  • 甘肃省妇幼保健院产二科 (兰州 730050 )

收稿日期: 2023-03-28

  网络出版日期: 2024-03-26

基金资助

甘肃省科技计划项目(22JR11RA176);兰州市第四批科技计划项目(2023-4-64)

Expression of lncRNA SNHG8 in placenta accreta and its effect on trophoblast invasion and migration

  • Li′na GAO ,
  • Xiaohui LIU ,
  • Yufang ZHANG ,
  • Xiaoling LIU ,
  • Xiaochun HE ,
  • Jing GAO ,
  • Li ZHANG ,
  • Jun SUN ,
  • Xiujuan WANG ,
  • Yan. DONG
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  • The Second Obstetrics Department,Gansu Provincial Marernity and Childcare Hospital,Lanzhou 730050,China

Received date: 2023-03-28

  Online published: 2024-03-26

摘要

目的 探讨lncRNA SNHG8在胎盘植入( placenta accreta,PA)中的表达及对滋养细胞侵袭迁移的影响。 方法 采用qRT-PCR检测PA组及对照组各30例胎盘组织中lncRNA SNHG8的表达,同时与30例PA患者产前超声评分做相关性分析。采用Transwell 和划痕实验检测干扰lncRNA SNHG8后对人绒毛膜滋养层细胞(HTR8/SVneo cells)侵袭和迁移的影响,同时,Western blot检测MMP-2和MMP-9的表达情况;StarBase软件预测lncRNA SNHG8下游靶点,并在两组胎盘组织中检测其表达;双荧光素酶报告实验检测lncRNA SNHG8与miR-542-3p的靶向关系。 结果 与对照组比较,lncRNA SNHG8在胎盘植入组胎盘组织中表达上调(P < 0.05),并与产前超声评分呈正相关。干扰lncRNA SNHG8后抑制了滋养细胞的侵袭迁移(P < 0.05),MMP-2及 MMP-9蛋白表达也明显下降(P < 0.05)。生物学预测miR-542-3p存在与lncRNA SNHG8的结合位点,miR-542-3p在PA胎盘组织中表达下调(P < 0.05),双荧光素酶报告实验证实lncRNA SNHG8能靶向调控miR-542-3p。共转染si-SNHG8与miR-542-3p inhibitor后,与si-SNHG8+inhibitor-NC相比,滋养细胞侵袭迁移能力增强(P < 0.05)。 结论 lncRNA SNHG8在PA胎盘组织中高表达并与其严重程度相关,lncRNA SNHG8通过调节miR-542-3p水平促进滋养细胞侵袭迁移行为学功能,提示lncRNA SNHG8在PA滋养细胞的侵袭迁移中发挥重要作用,有望成为临床诊断生物标记物和治疗靶点。

本文引用格式

高丽娜 , 刘小晖 , 张玉芳 , 刘小玲 , 何晓春 , 高晶 , 张莉 , 孙俊 , 王秀娟 , 董燕 . LncRNA SNHG8在胎盘植入的表达及其对滋养细胞侵袭及迁移的影响[J]. 实用医学杂志, 2024 , 40(5) : 646 -652 . DOI: 10.3969/j.issn.1006-5725.2024.05.010

Abstract

Objective To investigate the expression of lncRNA SNHG8 in placenta accrete (PA) and its effect on trophoblast invasion and migration. Methods qRT-PCR was used to detect the expression of lncRNA SNHG8 in placenta tissue of 30 cases in PA group and 30 cases in control group, and the correlation between lncRNA SNHG8 expression and prenatal ultrasound score of 30 cases in PA group was analyzed. Transwell and scratch assay were used to detect the effect of lncRNA SNHG8 interference on the invasion and migration of human chorionic trophoblast cells (HTR8/SVneo cells), and western blot was used to detect the expression of MMP-2 and MMP-9. The downstream targets of lncRNA SNHG8 were predicted by StarBase software, and the expression of lncRNA SNHG8 was detected in placental tissues of the two groups. Dual luciferase reporter assay was used to detect the targeting relationship between lncRNA SNHG8 and miR-542-3p. Results Compared with that of the control group, the expression of lncRNA SNHG8 was up-regulated in the placenta tissue of the PA group(P < 0.05), and it was positively correlated with prenatal ultrasound score. Interference with lncRNA SNHG8 inhibited the invasion and migration of trophoblast cells(P < 0.05); the protein expression of MMP-9 and MMP-2 also decreased significantly (P < 0.05). Biological prediction indicates that miR-542-3p had a binding site with lncRNA SNHG8, and miR-542-3p expression was down-regulated in PA placental tissue(P < 0.05). Dual luciferase reporter assay confirmed that lncRNA SNHG8 could target miR-542-3p. Compared with si-SNHG8+inhibitor-NC, co-transfection of si-SNHG8 and miR-542-3p inhibitor enhanced the invasion and migration ability of trophoblast cells(P < 0.05). Conclusion lncRNA SNHG8 is highly expressed in PA and is related to the severity of PA. LncRNA SNHG8 promotes the invasion and migration of trophoblast by regulating the level of miR-542-3p. The study suggests that lncRNA SNHG8 plays an important role in the invasion and migration of PA trophoblast cells, which is expected to be a clinical diagnostic biomarker and therapeutic target.

参考文献

1 WU X, YANG H, YU X, et al. The prenatal diagnostic indicators of placenta accreta spectrum disorders[J]. Heliyon, 2023,9(5):e16241. doi:10.1016/j.heliyon.2023.e16241
2 LI S C, LAN K C, HUNG H N, et al. HSPA4 Is a Biomarker of Placenta Accreta and Enhances the Angiogenesis Ability of Vessel Endothelial Cells[J]. Int J Mol Sci, 2022, 23(10):5682. doi:10.3390/ijms23105682
3 LIU X, WANG Y, WU Y, et al. What we know about placenta accreta spectrum (PAS)[J]. Eur J Obstet Gynecol Reprod Biol, 2021, 4(259): 81-89.
4 TAN J D, ZHOU M F, YANG S, et al. Long noncoding RNA HCP5 promotes osteosarcoma cell proliferation, invasion, and migration via the miR-29b-3p-LOXL2 axis[J]. Kaohsiung J Med Sci, 2022, 38(10): 960-970. doi:10.1002/kjm2.12577
5 WANG S, TAN B, XIAO L, et al. Gm10561Long non-coding RNA promotes myogenesis by sponging miR-432[J]. Epigenetics, 2022, 17(13): 2039-2055. doi:10.1080/15592294.2022.2105052
6 FU X, WU M, CHEN Y, et al. The expression profile of plasmatic exosomal lncRNAs in early-onset preeclampsia by sequencing[J]. Am J Transl Res, 2022, 14(6): 3806-3823.
7 WANG Y, CHENG Q, XIA Z, et al. Whole-transcriptome sequencing identifies key mRNAs, miRNAs, lncRNAs, and circRNAs associated with unexplained recurrent pregnancy loss[J].Cell Tissue Res, 2022, 389(1): 129-143. doi:10.1007/s00441-022-03632-x
8 LIPKA A, JASTRZEBSKI J P, PAUKSZTO L, et al. Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)[J]. Cells, 2021, 10(4):921. doi:10.3390/cells10040921
9 吴淑贞,张慧珊,刘雁,等. 胎盘植入组织lncRNA表达特征与ceRNA调控网络构建[J]. 南方医科大学学报,2019,39(10):1253-1259. doi:10.12122/j.issn.1673-4254.2019.10.19
10 陈敦金,杨慧霞. 胎盘植入诊治指南(2015)[J]. 中华产科急救电子杂志,2016,5(1):26-31.
11 ADU-BREDU T K, RIJKEN M J, CALVACHE A J N, et al. A simple guide to ultrasound screening for Placenta Accreta Spectrum for improving detection and optimizing management in resource limited settings[J]. Int J Gynaecol Obstet, 2023, 160(3): 732-741. doi:10.1002/ijgo.14376
12 BROOM M A, BAILEY E, KEARNS R J, et al. Diagnostic terminology in Placenta Accreta Spectrum: a scoping review[J]. Int J Obstet Anesth, 2022,8(51) :103572.
13 JAUNIAUX E, JURKOVIC D, HUSSEIN A M, et al. New insights into the etiopathology of placenta accreta spectrum[J]. Am J Obstet Gynecol, 2022,227(3):384-391. doi:10.1016/j.ajog.2022.02.038
14 CONTURIE C L, LYELL D J, Prenatal diagnosis of placenta accreta spectrum[J]. Curr Opin Obstet Gynecol, 2022, 34(2): 90-99. doi:10.1097/gco.0000000000000773
15 PANAITESCU A M, PELTECU G, BOTEZATU R, et al. Risk of Subsequent Hysterectomy after Expectant Management in the Treatment of Placenta Accreta Spectrum Disorders[J]. Medicina (Kaunas), 2022, 58(5):678. doi:10.3390/medicina58050678
16 WANG Z, CHEN J, SUN F, et al. LncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK in colorectal cancer[J]. Cell Biosci, 2022, 12(1): 120. doi:10.1186/s13578-022-00849-9
17 MAMIYA T, KANAMORI F, YOKOYAMA K, et al. Long noncoding RNA profile of the intracranial artery in patients with moyamoya disease[J]. J Neurosurg, 2022,138(3):709-716. doi:10.3171/2022.5.jns22579
18 GUO Y, GAO Y, LIU S. lncRNA XIST is associated with preeclampsia and mediates trophoblast cell invasion via miR-340-5p/KCNJ16 signaling pathway[J]. Transpl Immunol, 2022, 10(74): 101666.
19 张春婷,梁枭婷,王乐,等. 长链非编码RNA LINP1抑制DNA损伤促进非小细胞肺癌电离辐射抗性[J]. 实用医学杂志,2022,38(23):2908-2913. doi:10.3969/j.issn.1006-5725.2022.23.004
20 SHAN B, QU S, LV S, et al. YY1-induced long non-coding RNA small nucleolar RNA host gene 8 promotes the tumorigenesis of melanoma via the microRNA-656-3p/SERPINE1 mRNA binding protein 1 axis[J]. Bioengineered, 2022, 13(3): 4832-4843. doi:10.1080/21655979.2022.2034586
21 SONG H, SONG J, LU L, et al. SNHG8 is upregulated in esophageal squamous cell carcinoma and directly sponges microRNA-411 to increase oncogenicity by upregulating KPNA2[J]. Onco Targets Ther, 2021, 4(14): 4993-4994.
22 ZHANG P, LI S, CHEN Z, et al. LncRNA SNHG8 promotes proliferation and invasion of gastric cancer cells by targeting the miR-491/PDGFRA axis[J]. Hum Cell, 2020, 33(1): 123-130. doi:10.1007/s13577-019-00290-0
23 FAN D, QIU B, YANG X J, et al. LncRNA SNHG8 promotes cell migration and invasion in breast cancer cell through miR-634/ZBTB20 axis[J]. Eur Rev Med Pharmacol Sci, 2020, 24(22): 11639-11649.
24 WEI X, YUAN Y, YANG Q, Long noncoding RNA PVT1 accelerates the growth of placental trophoblasts in preeclampsia through the microRNA-24-3p/HSD11B2 axis[J]. Mol Reprod Dev, 2022, 89(7): 271-280. doi:10.1002/mrd.23575
25 WEI X, YUAN Y, YANG Q. SNHG22 promotes migration and invasion of trophoblasts via miR-128-3p/PCDH11X axis and activates PI3K/Akt signaling pathway[J]. Clinics (Sao Paulo), 2022, 6(77): 100055.
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